cssi/SciSciGPT-SciSciNet huggingface dataset:
Unconventional Nuclides for Radiopharmaceuticals

Rapid and widespread growth in the use of nuclear medicine for both diagnosis and therapy of disease has been the driving force behind burgeoning research interests in the design of novel radiopharmaceuticals. Until recently, the majority of clinical and basic science research has focused on the development of 11C-, 13N-, 15O-, and 18F-radiopharmaceuticals for use with positron emission tomography (PET) and 99mTc-labeled agents for use with single-photon emission computed tomography (SPECT). With the increased availability of small, low-energy cyclotrons and improvements in both cyclotron targetry and purification chemistries, the use of "nonstandard" radionuclides is becoming more prevalent. This brief review describes the physical characteristics of 60 radionuclides, including beta+, beta-, gamma-ray, and alpha-particle emitters, which have the potential for use in the design and synthesis of the next generation of diagnostic and/or radiotherapeutic drugs. As the decay processes of many of the radionuclides described herein involve emission of high-energy gamma-rays, relevant shielding and radiation safety issues are also considered. In particular, the properties and safety considerations associated with the increasingly prevalent PET nuclides 64Cu, 68Ga, 86Y, 89Zr, and 124I are discussed.
Prostate cancer ETS rearrangements switch a cell migration gene expression program from RAS/ERK to PI3K/AKT regulation

Background The RAS/ERK and PI3K/AKT pathways induce oncogenic gene expression programs and are commonly activated together in cancer cells. Often, RAS/ERK signaling is activated by mutation of the RAS or RAF oncogenes, and PI3K/AKT is activated by loss of the tumor suppressor PTEN. In prostate cancer, PTEN deletions are common, but, unlike other carcinomas, RAS and RAF mutations are rare. We have previously shown that over-expression of “oncogenic” ETS transcription factors, which occurs in about one-half of prostate tumors due to chromosome rearrangement, can bypass the need for RAS/ERK signaling in the activation of a cell migration gene expression program. In this study we test the role of RAS/ERK and PI3K/AKT signaling in the function of oncogenic ETS proteins.
Role of IL-6 and TNF in thermoregulation and survival during sepsis in mice

Interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) have been implicated as key mediators in inflammation, morbidity, and mortality associated with sepsis. We examined the role of IL-6 and TNF...
Influences of parasites and thermoregulation on grouping tendencies in marine iguanas

I determined whether grouping behavior influences parasite load and body temperature of Galapagos marine iguanas, reptiles that rest gregariously. Mobile (or predatory) Ornithodoros ticks (4.7 mm average body length) approached at a ground speed of 65 cm/min and parasitized sleeping marine iguanas for 3.7 h per night, drawing about 0.1 ml blood. Contagiously transmitted Amblyomma ticks hang on to iguana hosts for days or weeks. Marine iguanas sleeping alone had 2.0 mobile ticks per night, while individuals sleeping in groups had 0.1 to 1.1 mobile ticks per night. Single iguanas decreased their mobile parasite load to 0.2 ticks per night by sleeping on bushes. Experimental nightly translocation of iguanas to areas without other sleeping iguanas significantly increased their mobile parasite burden above levels encountered by naturally single individuals (n 5 4.6 ticks per night). Creating an experimental group of two animals reduced infestation with mobile ticks by 59% compared to levels on single animals. Over the course of weeks, mobile ectoparasite loads at grouping sites increased to levels found at single sites, at which point marine iguanas changed sleeping sites. Grouping had no effect on the prevalence of contagious ticks. Furthermore, grouping did not help to conserve body temperature in Genovesa iguanas, as measured by radiotelemetry. I conclude that marine iguanas group during daytime at microhabitats favored for thermoregulation (predation is absent in this population). Thermoregulation was not of prime importance for nightly aggregations, which instead served to reduce mobile ectoparasite load. As a minimum cost of infestation, I estimate that individuals sleeping alone would have a 5.4% lower annual energy budget due to tissue removal, not including potential internal infections.
Polarization measurements using a commercial off-the-shelf digital camera

This paper presents a methodology to obtain polarization profiles using a commercial off-the-shelf (COTS) digital camera. It contains calibration techniques to ensure robust and accurate determination of the Stokes parameters and the system polarization state. It calculates the Stokes parameters for each scene pixel along with the degree of polarization, azimuth, and ellipticity angles for each of the RGB channels. A detailed calculation shows that the quasimonochromatic approximation for the wavelength dependence of the quarterwave plate can be extended to include the broadband RGB channels. A simple and inexpensive camera calibration converts RGB values to optical density and then to relative intensity values. An analysis is presented for the wavelength-dependent response of the tuned zero-order quartz quarterwave retarder, the broadband RGB channels, and the fourth Stokes parameter. The noise characteristics of the digital camera are analyzed along with a detailed calibration of the imagery for target characterization applications. An extensive validation process, using white light, compares calculated theoretical results with the empirical results from the COTS camera. A RGB pseudocoloring scheme, related to the Poincare sphere, is introduced for the visualization of polarization parameters of daylight scenes.
Drift and Pluralization in International Trade

In recent years, a considerable body of literature has dealt with relations between the so-called developed and developing nations. More recently, a number of analysts have attempted to gain leverage over the problem by utilizing a systemic perspective that links centers and peripheries.1 A basic hypothesis suggests a relationship of drift, in which the more and the less developed nations seem to be moving further apart. In particular, Jorge Dominguez in a recent article hypothesized that there is an "increasing economic fragmentation between the countries of the center and the peripheries." Dominguez verified the hypothesis by comparing trade over time, utilizing two types of statistics: an index of relative acceptance (RA), and two indices of economic importance (EIp and EIc).2 We believe that relations are somewhat more complex than a simple drift hypothesis suggests. Dominguez's research emphasized the relaxation in relations between nations formerly bound by bilateral colonial ties. Although Dominguez included twelve countries in his definition of the center, he only presented data supporting drift between the single most dominant center nation and a peripheral region, for example, between Morocco and France, Tunisia and France. We suggest that individual cases of drift go together with a more general pattern of pluralization. Within this larger frame, specific
Mode of Centriole Duplication and Distribution

Centriole stability and distribution during the mammalian cell cycle was studied by microinjecting biotinylated tubulin into early G1 cells and analyzing the pattern of incorporation into centrioles. Cells were extracted and cold treated to depolymerize labile microtubules, allowing the fluorescent microscopic visualization of the stable centrioles. The ability to detect single centrioles was confirmed by use of correlative electron microscopy. Indirect hapten and immunofluorescent labeling of biotinylated and total tubulin permitted us to distinguish newly formed from preexisting centrioles. Daughter centrioles incorporated biotinylated tubulin, and at mitosis each cell received a centrosome containing one new and one old centriole. We conclude that in each cell cycle tubulin incorporation into centrioles is conservative, and centriole distribution is semiconservative.
Sonographic Findings in Fetal Alpha Thalassemia Major

Alpha thalassemia major is an autosomal recessive disease found mostly in Southern Chinese and Southeast Asians. It is caused by deletion of alpha globin genes. Normally, there are four alpha genes. 1Some cases lead to lifelong dependence on transfusions, with iron buildup and shortened life duration. Depending on the number of genes affected, the fetus may die in utero or very soon after birth.2
Perceptions of effective professional behavior feedback: occupational therapy student voices.

The purpose of this study was to gather formative evaluation data to determine students? perceptions of effective aspects of professional behavior feedback for use in program development. A qualitative design was used to gather data from baccalaureate-level occupational therapy students. Through focus groups and semi-structured interviews, data were gathered about the students? beliefs, feelings, and recommendations for policy changes. Four themes emerged: Not Just "Contact With a Piece of Paper"; Fieldwork Needs To Be Taken Into Account; Faculty Fairness and Support Need To Be Present; "This Is Like Therapy for Me." Aspects of these themes have implications for classroom and fieldwork settings. The type of feedback these students found helpful and the desire to have fieldwork performance considered along with their classroom behavior were salient perceptions. As educators, it is important to listen to the voices of students to gain insights into their perceptions of the effective aspects of the feedback process for professional behaviors
TAT Protein Transduction Into Isolated Perfused Hearts TAT–Apoptosis Repressor With Caspase Recruitment Domain Is Cardioprotective

Background— Linkage of the 11–amino-acid transduction domain of HIV TAT to a heterologous protein allows the protein to be transduced readily into cells. Methods and Results— In this study, we inserted the apoptosis repressor with caspase recruitment domain (ARC) or β-galactosidase (β-gal) cDNA into the pTAT-hemagglutinin bacterial expression vector to produce genetic in-frame TAT-ARC or TAT-β-gal fusion proteins for use in cell culture and in Langendorff perfusion of adult rat hearts. TAT-β-gal and TAT-ARC were conjugated with Texas Red and could be detected in >95% of cells. TAT-ARC was able to protect H9c2 cells against cell death mediated by hydrogen peroxide, as measured by protection against the loss of mitochondrial membrane potential and preservation of nuclear morphology. Isolated adult hearts were perfused with recombinant TAT-β-gal or TAT-ARC (20 nmol/L) for 15 minutes and then subjected to 30 minutes of global no-flow ischemia, followed by 2 hours of reperfusion. Protein transduction was asses...
Mutations Altering the N-Terminal Receiver Domain of NRI (NtrC) That Prevent Dephosphorylation by the NRII-PII Complex in Escherichia coli

The phosphorylated form of NRI is the transcriptional activator of nitrogen-regulated genes in Escherichia coli . NRI∼P displays a slow autophosphatase activity and is rapidly dephosphorylated by the complex of the NRII and PII signal transduction proteins. Here we describe the isolation of two mutations, causing the alterations ΔD10 and K104Q in the receiver domain of NRI, that were selected as conferring resistance to dephosphorylation by the NRII-PII complex. The mutations, which alter highly conserved residues near the D54 site of phosphorylation in the NRI receiver domain, resulted in elevated expression of nitrogen-regulated genes under nitrogen-rich conditions. The altered NRI receiver domains were phosphorylated by NRII in vitro but were defective in dephosphorylation. The ΔD10 receiver domain retained normal autophosphatase activity but was resistant to dephosphorylation by the NRII-PII complex. The K104Q receiver domain lacked both the autophosphatase activity and the ability to be dephosphorylated by the NRII-PII complex. The properties of these altered proteins are consistent with the hypothesis that the NRII-PII complex is not a true phosphatase but rather collaborates with NRI≈P to bring about its dephosphorylation.
Evaluating the impact of California's full service partnership program using a multidimensional measure of outcomes.

This study evaluates the impact of California’s full-service partnership (FSP) program using a multidimensional measure of outcomes. The FSP program is a key part of California’s 2005 Mental Health Services Act. Secondary data were collected from the Consumer Perception Survey, the Client and Service Information System, and the Data Collection and Reporting System, all data systems which are maintained by the California Department of Mental Health. The analytic sample contained 39,681 observations of which 588 were FSP participants (seven repeated cross-sections from May 2005 to May 2008). We performed instrumental variables (IV) limited information maximum likelihood and IV Tobit analyses. The marginal monthly improvement in outcomes of services for FSP participants was approximately 3.5 % higher than those receiving usual care with the outcomes of the average individual in the program improving by 33.4 %. This shows that the FSP program is causally effective in improving outcomes among the seriously mentally ill.
Comparison of self-reported injection frequencies for past 30 days and 6 months among intravenous drug users

Abstract In this study we compared two parallel self-reported measures that now are being used to assess the recent frequency of intravenous drug use. The study sample consisted of 926 HIV seronegative drug users recruited for participation in HIV research. During a standard interview with each drug user, we first asked about injections in the past 30 days, and then about injections in the past .6 months. The correlation between reports on the past 6 months and the past 30 days was appreciable when all injections were considered (Spearman correlation coefficient ϱ = 0.78). It increased when the sample was restricted to subjects who reported injections in the past month (ϱ = 0.88). This restriction resulted in a 15% reduction of the sample size, since 137 participants reported drug use in the previous 6 months but not in the previous 30 days. Concordance tended to be slightly higher for reported frequencies of heroin injections than for cocaine injections, and for men as compared to women. The observed levels of concordance indicate that in many instances both approaches can yield comparable results. Nevertheless the choice of 30 days recall vs 6 months recall must rest upon the specific research questions of each investigation.
Financial Constraints and Trade Credit as a Strategic Tool: Evidence from Small-Scale Reservation Reforms in India

Do incumbent supplier firms facing increased threat of entry by competitors adjust trade credit to respond to such threats? Threatened incumbent supplier firms may extend more trade credit, ex-ante, to defend their market power, or they may reduce trade credit as enforcement of such informal credit contracts is expected to become more difficult with the expected decline in market power. I test these contrasting predictions by exploiting plausibly exogenous, staggered removals of product level entry barriers for Indian manufacturing firms, and find that an average incumbent supplier firm extends 10% more trade credit with increased threat of entry, supporting the first hypothesis. My results are particularly strong for firms manufacturing differentiated products, where reduction in price mark-ups may not be an effective strategy, thereby bringing into focus the role of trade credit as a strategic tool to defend market power.
Microbiology and Biochemistry of Methanogenesis, A Selected Review

This selected review of the methanogenic fermentation encompasses a brief examination of the difficulties encountered by early microbiologists as background for discussing current concepts of microbiological interactions between methanogenic and non-methanogenic organisms. Some of the basic findings uncovered by modern workers help to explain culturing difficulties as well as problems associated with the types of presumed methanogenic substrates chosen. The importance of “interspecies H2 transfer” as it relates to the mixed fermentation typical of anaerobic digesters is reviewed. The final section is devoted to a review of the unique cofactors and enzymes characteristic of the metnanogenic bacteria.
They Didn't Join the Band: Disaffected Women in Revolutionary Philadelphia

The first anniversary of American independence in Philadelphia, as chronicled by The Pennsylvania Gazette, was celebrated on July 4, 1777, with "demonstrations of joy and festivity." The holiday schedule got under way at noon with a display of ships and gallies on the river "dressed in the gayest manner," each of which fired thir teen times. Triple discharges of cannon followed the nautical salutes. Loud huzzas resounded throughout the city while a brigade of North Carolina troops accompa nied by a corps of mounted soldiers and artillerymen marched down Second Street. Evening brought on the ringing of Philadelphia's bells and night closed in with a "grand exhibition of fireworks" whose glow bathed a united community. The news paper report concluded that "everything was conducted with the greatest order and decorum and the face of joy and gladness was universal."1 This description of America's first anniversary of the Fourth of July would not be unfamiliar to Philadelphians today, or for that matter, to most Americans. The noise, the color, the parades, the fireworks?all these have been consistent fixtures of Independence celebrations down to the present day. The unanimity of sentiment, however, so prominently featured in the first anniversary account, masked a number of citizens' ambivalence or outright hostility concerning the Fourth of July message. One such citizen wrote a very different description of exactly the same day in 1777:
Defining the Real Estate Body of Knowledge: A Survey Approach

Executive Summary. This article analyzes the results of a survey sent to real estate academics and professionals around the world, attempting to define a body of knowledge for real estate. A list o...
Racecourse fracture management. Part 3: Emergency care of specific fractures

Summary In consideration of first aid of appendicular fractures in the horse, the literature is inconsistent and in some cases wrong or misleading. This in large part is due to misunderstanding of fracture mechanics and this paper aims to give a contemporary review of the subject. It is particularly relevant for fractures that occur on the racecourse or in horses in training which, due to their aetiopathogenesis, have substantial site and configuration commonality. However, the techniques discussed are frequently also applicable to non-racing injuries. Clinical features are important in assessing horses on the racecourse when imaging techniques are limited. This paper highlights these in order to guide decision making.
On Guanidinium and Cellular Uptake

Guanidinium-rich scaffolds facilitate cellular translocation and delivery of bioactive cargos through biological barriers. Although impressive uptake has been demonstrated for nonoligomeric and nonpept(o)idic guanidinylated scaffolds in cell cultures and animal models, the fundamental understanding of these processes is lacking. Charge pairing and hydrogen bonding with cell surface counterparts have been proposed, but their exact role remains putative. The impact of the number and spatial relationships of the guanidinium groups on delivery and organelle/organ localization is yet to be established.
WOMEN IN THE EARLY YEARS OF THE AMERICAN SOCIETY OF MAMMALOGISTS (1919-1949)

During the first 30 years of The American Society of Mammalogists (ASM), a small but notable group of women made significant contributions to the Society and to mammalogy in general. The limited opportunity for women in mammalogy at the time of the founding of the ASM in 1919 is evidenced by the observation that only 16 of 435 Charter Members were women. To highlight the contributions of early women mammalogists, we describe the accomplishments of 23 women in short biographical treatments. To facilitate our presentations of activities and accomplishments, each woman was placed into one of six categories, although some individuals could have been listed under more than one category. The six categories were research in the field, research in the museum, research in the laboratory, service to the ASM, other naturalists involved in the ASM, and relevant non-members.
Using Rank-Order Measures to Represent Continuous Variables

The correlations between rank-order measures and their underlying scores, sampled from continuous distributions, are obtained for various numbers of categories in eight different distributions. The purpose is to assess the amount of distortion which results when researchers have only rank-order measures of underlying continuous level variables. Both the number of rankorder categories and the nature of the underlying distribution are found to be important determinants of the degree of distortion. Further, the relationship between the number of rank-order categories and the degree of distortion depends on the nature of the underlying distribution. The results of this analysis are then compared with those based on Stuart's work (a) and Abelson and Tukey (a, b) (which are found to overestimate the degree of distortion) and Labovitz (which are found to underestimate the degree of distortion). The results of this analysis are then generalized and their implications for the use of rank-order measures of underlying continuous level variables are explored. Several studies have examined the correlation between samples of scores from continuous distributions and their rank-order scores. These studies are important for social scientists because of the insights they provide about loss of information, or degree of distortion, resulting from the use of rank-order measures to represent continuous underlying variables. The issue is crucial, since many of the variables used in the social sciences may be assumed to have a continuous underlying distribution, even though our measures of them are only ordinal. For example, although "political stability" and "democratization" may each be conceived of as having continuous underlying distributions, ranging from low to high, we may have only rank-order measures of these variables. However, if these ordinal measures could substitute for the underlying continuous variable without greatly distorting zero-order correlations, they would provide for the multivariate analysis of ordinal data through the "parametric strategy" (Kim).'
PRACTICE NOTES: Breast Cancer Prevention Strategies for Aged Black Lesbian Women

Recognizing that effective intervention must include models of treatment that “meet clients where they are,” this paper describes culturally sensitive breast cancer prevention strategies that may be useful for health care providers in an effort to reach a triple-minority population: Black, lesbian women. The strategies are an adapted version of the Witnessing In Tennessee (WIT) model. WIT was developed to increase early detection of breast cancer among Black women. The strategies have been adapted for use among Black, aged, lesbian women. This model provides practitioners with universal techniques that can be used to address various health disparities.
Differential effects of goal cues on everyday action errors in Alzheimer's disease versus Parkinson's disease dementia.

OBJECTIVE Prior research has shown that individuals with Parkinson's disease dementia (PDD) show a different pattern of error types on everyday tasks compared with individuals with Alzheimer's disease (AD). This study evaluated whether these groups would respond differently to cues designed to remind participants of task goals and improve performance of everyday tasks (i.e., goal cues). METHOD Participants with PDD (n = 20) and AD (n = 20), and a comparison group of individuals with Parkinson's disease and no dementia (n = 20), were administered performance-based tasks of everyday functioning that allowed for the quantification of errors before and after the presentation of goal cues. RESULTS AD participants showed a significantly greater response to the goal cues as compared with individuals with PDD. The goal cues facilitated the completion of task goals but did not promote error correction (i.e., the undoing of errors that had been made earlier during the task). CONCLUSIONS Not all dementia patients respond similarly to cues designed to improve everyday functioning. Understanding patients' specific form of everyday action impairment is crucial for developing individualized interventions that target specific functional deficits.
On the Excited State Energy Surface of Rhodopsin and Bacteriorhodopsin

Recently, LEWIS has proposed a molecular mechanism of excitation in visual transduction and bacteriorhodopsin [1]. There are three essential elements in this mechanism: (1) Vertical excitation of the retinal chromophore produces electron density rearrangement. (2) A bond rearrangement in the protein lowers the energy of this excited retinal-protein complex. (3) Torsional motion and rearrangement of the chromophore couples the molecule back onto the ground state surface and stabilizes the new protein conformation.
Species Composition and Diversity of Avian in Tianjin

The avian of Tianjin were surveyed from 2002 to 2005,with the systematic sampling,line transect and point count methods.A total of 389 species representing 19 orders,68 families and 184 genera were recorded.Of the total species,203(52.19%) species distribute in the Palaeartic realm,42(10.79%) species in the Oriental realm and 144(37.02%) species distribute widely.There are 234 species(60.15%) of travelers,74 species(19.02%) of summer residents,55 species(14.14%) of residents and 26 species(6.68%) of winter residents.Based on the G-F diversity index,the highest avian diversity of 0.76 was in wetland,the lowest of 0.58 was in habitat city park,and the diversities in mountain and cultivated land were similar(0.75).The results showed that the distribution of species composition and diversity of avian was correlated to the characteristics of Tianjin environment.
Day-ahead coordinated operation of utility-scale electricity and natural gas networks considering demand response based virtual power plants

Abstract The steady-state coordinated operation of electricity networks and natural gas networks to maximize profits is investigated under market paradigm considering demand response. The components in its gas supply networks are modeled and linearized under steady-state operating conditions where combined cycle gas turbine (CCGT) generators consume natural gas and offer to the electricity market. Interruptible-load based and coupon-based demand response virtual power plants are considered trading in the market like physical generators. A bi-level programming optimization model is formulated with its upper-level representing the coordinated operation to maximize profits and its lower-level simulating the day-ahead market clearing process. This bi-level problem is formulated as a mathematical program with equilibrium constraints, and is linearized as a mixed-integer programming problem. Case studies on a 6-bus power system with a 7-node natural gas system and an IEEE 118-bus power system with a 14-node gas system verify the effectiveness of the coordinated operation model. The impacts of demand response based virtual power plants on the interactions between the two networks are also analyzed.
Genetic and grade and tonnage models for sandstone-hosted roll-type uranium deposits, Texas Coastal Plain, USA

Abstract The coincidence of a number of geologic and climatic factors combined to create conditions favorable for the development of mineable concentrations of uranium hosted by Eocene through Pliocene sandstones in the Texas Coastal Plain. Here 254 uranium occurrences, including 169 deposits, 73 prospects, 6 showings and 4 anomalies, have been identified. About 80 million pounds of U3O8 have been produced and about 60 million pounds of identified producible U3O8 remain in place. The development of economic roll-type uranium deposits requires a source, large-scale transport of uranium in groundwater, and deposition in reducing zones within a sedimentary sequence. The weight of the evidence supports a source from thick sequences of volcanic ash and volcaniclastic sediment derived mostly from the Trans-Pecos volcanic field and Sierra Madre Occidental that lie west of the region. The thickest accumulations of source material were deposited and preserved south and west of the San Marcos arch in the Catahoula Formation. By the early Oligocene, a formerly uniformly subtropical climate along the Gulf Coast transitioned to a zoned climate in which the southwestern portion of Texas Coastal Plain was dry, and the eastern portion humid. The more arid climate in the southwestern area supported weathering of volcanic ash source rocks during pedogenesis and early diagenesis, concentration of uranium in groundwater and movement through host sediments. During the middle Tertiary Era, abundant clastic sediments were deposited in thick sequences by bed-load dominated fluvial systems in long-lived channel complexes that provided transmissive conduits favoring transport of uranium-rich groundwater. Groundwater transported uranium through permeable sandstones that were hydrologically connected with source rocks, commonly across formation boundaries driven by isostatic loading and eustatic sea level changes. Uranium roll fronts formed as a result of the interaction of uranium-rich groundwater with either (1) organic-rich debris adjacent to large long-lived fluvial channels and barrier–bar sequences or (2) extrinsic reductants entrained in formation water or discrete gas that migrated into host units via faults and along the flanks of salt domes and shale diapirs. The southwestern portion of the region, the Rio Grande embayment, contains all the necessary factors required for roll-type uranium deposits. However, the eastern portion of the region, the Houston embayment, is challenged by a humid environment and a lack of source rock and transmissive units, which may combine to preclude the deposition of economic deposits. A grade and tonnage model for the Texas Coastal Plain shows that the Texas deposits represent a lower tonnage subset of roll-type deposits that occur around the world, and required aggregation of production centers into deposits based on geologic interpretation for the purpose of conducting a quantitative mineral resource assessment.
Abstract 21: The mTORC2 target Akt is regulated in response to glutamine metabolite levels

Highly proliferating cells are particularly dependent on glucose and glutamine for bioenergetics and to fuel biosynthesis of macromolecules. The signals that respond to the fluctuations of these nutrients and how they control metabolic pathways remain poorly understood. mTOR, as part of mTOR complex 1 (mTORC1), responds to amino acids and plays a central role in metabolism. On the other hand, little is known on how mTORC2, consisting of the core components mTOR, rictor, SIN1 and mLST8 is regulated and its metabolic functions. The phosphorylation of the mTORC2 substrate, Akt, is enhanced in cancer cells, suggesting that mTORC2 becomes deregulated during tumorigenesis. Here we found that the activity of mTORC2 is enhanced by diminishing glutamine-derived metabolites. mTORC2 activity is required by glutamine-requiring biosynthetic pathways such as the hexosamine biosynthetic pathway (HBP). Acute nutrient withdrawal augments Akt phosphorylation but does not affect GFAT1 expression. However, extreme starvation that eventually depletes intracellular glutamine metabolites inactivates mTORC2 and downregulates GFAT1 expression. Thus, while mTORC1 senses glutamine abundance to promote anabolism, mTORC2 responds to declining glutamine catabolites in order to restore metabolic homeostasis. Our findings uncover the role of mTORC2 in metabolic reprogramming and provide insights on more effective therapeutic strategies for glutamine-dependent tumors. Citation Format: Estela Jacinto, Joseph Moloughney, Peter K. Kim, Nicole M. Vega-Cotto, Chang-Chih Wu, Thomas Lynch, Sisi Zhang, Matthew Adlam, Sai Guntaka, Po-Chien Chou, Joshua D. Rabinowitz, Guy Werlen. The mTORC2 target Akt is regulated in response to glutamine metabolite levels. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 21.
Abstract A65: Immune modulation of natural killer cell adoptive transfer for the treatment of Osteosarcoma lung metastastasis: Targeting the PD-1/ PDL-1 signaling pathway

Osteosarcoma (OS) is the most common primary malignant bone tumor in children. Pulmonary metastasis is the major cause of mortality in OS patients with a 25-30 % 5-year survival rate. Therefore, development of novel targeted approaches like immunotherapy has been the interest of investigators. Previously, we have demonstrated that Liposomal muramyl tripeptipe phosphatidyl ethanolamine (L-MTP-PE) reduced the metastatic burden in animal models and caused an 8% improvement in the overall survival of patients with OS metastatic disease through macrophage activation. The adoptive transfer of mature natural killer (NK) cells activated ex vivo has exhibited anti-tumor efficacy in breast cancer and lymphoma models. It has been shown that NK cells exert cytotoxicity against OS cells in vitro. Aerosolized interleukin 2 (IL-2) administered to dogs with OS lung disease has demonstrated therapeutic benefit. Additionally, Guma S. R. et al. showed that aerosol IL-2 enhanced the efficacy of infused NK cells against OS lung metastasis in vivo. Aerosol IL-2 and NK cell combination therapy resulted in the regression of OS lung metastasis through enhanced tumor cell apoptosis. Moreover, the combination therapy significantly increased the overall survival of mice with OS lung metastases. However, the treatment is not curative as metastasis persists leading to relapse. Recent studies have demonstrated the immunosuppressive role of checkpoint inhibitors such as programmed death receptor 1 (PD-1) and its ligand, programmed death ligand 1 (PDL-1). Inhibition of the PD-1/PDL-1 pathway has shown immunotherapeutic benefit in lung and renal tumors. Involvement of this pathway in OS lung metastases is unknown. Therefore, based on our previous studies of aerosol IL-2, we hypothesize that aerosol IL-2 causes upregulation of PDL-1 expression on OS tumor cells, which in turn interacts with PD-1 receptor on NK cells, restricting NK cells9 killing ability against OS. Our preliminary data demonstrates high PDL-1 expression in human OS cells and OS lung metastases from patients. Using a human OS mouse model, we further show that aerosol IL-2 enhances PDL-1 expression in OS lung metastases. PDL-1 expression on OS lung nodules was observed towards the tumor periphery. Hence, we propose that targeting the PD-1/ PDL-1 axis using anti-PD-1 antibody will enhance the efficacy of NK cell-directed therapy, in the presence or absence of IL-2, against OS lung metastasis and improve the overall survival. Citation Format: Pooja M. Dhupkar, Eugenie Kleinerman, Nancy Gordon. Immune modulation of natural killer cell adoptive transfer for the treatment of Osteosarcoma lung metastastasis: Targeting the PD-1/ PDL-1 signaling pathway. [abstract]. In: Proceedings of the AACR Special Conference: Tumor Immunology and Immunotherapy: A New Chapter; December 1-4, 2014; Orlando, FL. Philadelphia (PA): AACR; Cancer Immunol Res 2015;3(10 Suppl):Abstract nr A65.
Networks of Criminality: The State and Crime Policy in Contemporary Democracy

espanolWhy do so many security policies fail in Latin America? This article shows that itis difficult to uproot criminality because it is an inherent part of the development of both states and democratic regimes. More specifically, it is part of the three main networks of security providers: the executive branch; the criminal justice system; and the sector of armed non-state entities. Relations within and between these three networks reflect their own interests and powers rather than public security, undermining policy from the beginning. This article will apply this analytical framework to two principal dimensions of public security in Latin America. One is of illegally trafficked goods, such as narcotics; the specific case study here is of the trafficking of firearms. The second dimension is the set of security policies in a country, which range from iron fist crackdowns to community policing. The case study is Honduras, which has endured nearly every security problem that afflicts the region, respondingwith policies that failed for 15 years until they began to shift attention toward the networks of criminality that were obstructing them. portuguesPorque fracassam muitas politicas criminais nas democracias latino-americanas? Este artigo mostra que e dificil de desarraigar a criminalidade porque e um elemento ao centro do desenvolvimento do estado e o regime democratico. Especificamente, e parte das tres redes principais dos fornecedores de seguranca: o poder executivo; o sistema de justica criminal; e a rede de grupos armados nao estatais. As relacoes dentro de e entre estas redes refletem os seus interesses e poderes em vez da inseguranca publica, entorpecendo as politicas de seguranca desde o principio. Aplica-se esta analise em duas areas principais de seguranca publica. Um e contra um bem (como as drogas) que uma fonte de atividade ilegal; o seu caso de estudo e o trafico de armas de fogo. Outra dimensao e a rama de politicas de seguranca nacional, desde a mao dura ate a policia comunitaria. O caso do estudo e a Honduras, um pais que tem sofrido de todos os problemas de seguranca com politicas de seguranca que tem fracassado por 15 anos, antes de que se mudara o seu foco nas redes de criminalidade.
The National Joker: Abraham Lincoln and the Politics of Satire Todd Nathan Thompson. Carbondale: Southern Illinois University Press, 2015.

The National Joker: Abraham Lincoln and the Politics of Satire Todd Nathan Thompson. Carbondale: Southern Illinois University Press, 2015.Todd Nathan Thompson examines Lincoln's political image. In essence, Lincoln's self-deprecation rendered his critics' satires harmless: his "folksy, fallible figure" (2) seemed impervious to the kind of caricature that leveled and even destroyed his more pompous contemporary rivals.Thompson distinguishes satire from humor: the former belittles its targets by exaggerating stereotypical behavior or appearance; the latter amuses its audience by exaggerating the foibles of human nature. By poking fun at pompous men, satire effectively undercut the presidential aspirations of Senator Stephen A. Douglas and General George B. McClellan. But by poking fun at a self-confessed frontier rustic, satire ironically helped forward the candidacy of a common man.Lincoln's reputation as a storyteller preceded him. If a political cartoon included the caption, "This reminds me of a little story," readers instantly recognized Lincoln as its speaker. A parabolic storyteller, he was famous for repurposing even apolitical anecdotes for political purposes. For instance, in an Aesop fable, a lion foolishly has his claws and teeth removed at the request of a sly woodsman (father of the girl the lion was courting). When he saw the lion was disarmed, the woodsman easily beat out the lion's brains. Lincoln retold the story to someone advising him that the best way to avoid a civil war was to surrender federal forts in the South. "May it not be so," Lincoln said, "with me, if I give up all that is asked" (13).Lincoln used "satiric modesty" rhetorically to expose the pretentions of his opponents. For instance, in 1848, when running against a former general who styled himself a war hero, Lincoln would exaggerate his own supposedly unglamorous record in the Black Hawk War. This underdog strategy made the self-proclaimed hero seem a braggart. Later, during the 1858 Lincoln-Douglas debates, six-foot four-inch Lincoln played off the much-touted prominence of his opponent by repeatedly calling five-foot four-inch Douglas a "giant, good man." Audiences got the joke. Lincoln was satirizing Douglas's somewhat precious way of describing himself as the "little big man."Why didn't the joke backfire on Lincoln? Whereas Douglas was touchy and self-defensive about his shortness, Lincoln made fun of his own awkward height (eight inches taller than the average American). …
Steroid Hormone Structure, Receptor Binding and Activity: Empirical Drug Design

Steroid hormones play a vital role in a wide variety of essential physiological processes including cell growth, sexual development, maintenance of salt balance and sugar metabolism. Because of the key role that steroids play in human health and disease therapy, an understanding of the molecular details of steroid hormone action is essential. Small changes in the number and position of functional groups on the steroid nucleus result in large differences in activity. Many of these processes are known to be dependent upon initial binding of the steroid to a specific cytosolic protein receptor and the subsequent interaction of the steroid-receptor complex with chromatin [1]. An examination of the three-dimensional shapes of the hormones, antihormones, chemicals and the drugs that compete for a common binding site on a specific receptor binding protein or metabolizing enzyme can provide information on structural features that influence hormonal response. Crystallographic data on over 1000 steroids [2,3] provide information concerning preferred conformations, relative stabilities and substituent influence on the interactive potential of steroid hormones and analogs. Systematic conformational analysis of subsets of these data having common structural features suggests that steroids crystallize in global minimum energy conformations or local minimum energy conformations that are less than two kcal mol-1 above the global minimum [4–6]
Comparison of the Structural Response to Pressure of Ionic Liquids with Ether and Alkyl Functionalities

The response of ionic liquids to external perturbations including elevated pressure is a topic of current interest for applications such as tribology. Ionic liquids come in many classes, including those that are amphiphilic and some that are mostly polar having either cationic or anionic tails that are functionalized. The current study compares the effect of elevated pressure on two ionic liquids with different types of cationic tail. 1-Decyl-3-methylimidazolium bis(trifluoromethylsulfonyl)amide (C10mim+/NTf2–) is amphiphilic whereas isoelectronic ether-functionalized 1-(2-(2-(2-methoxyethoxy)ethoxy)ethyl)-3-methylimidazolium bis(trifluoromethylsulfonyl)amide (C7O3mim+/NTf2–) has cationic tails that are more polar and conformationally different. We find that the response to elevated pressure for these two systems is quite unsimilar. Intramolecular conformational changes as well as changes in the structure of liquid nanodomains appear to be significantly more prominent in the case of C10mim+/NTf2–. Whereas...
Narrating Tazmamart: visceral contestations of Morocco’s transitional justice and democracy

ABSTRACTThis article argues that Tazmamart narratives, relating the experience of Moroccan inmates disappeared and unlawfully detained for eighteen years in a secret camp, are exemplary within literary and visual accounts of the Years of Lead. Despite their different styles, genre, and media, stories inspired by Morocco’s most hostile detention and torture centres under King Hassan II’s reign (1961–1999) form a distinct ensemble that encompasses significant issues pertinent to the discussion of the country’s dark past and its memorialisation. Memoirs, fictionalised memoirs, and documentaries produced by survivors, activists, and cultural actors and their reception pose urgent questions that haunt Morocco’s post-Years of Lead transitional democracy and justice: who has the right to tell stories of sate sponsored human rights abuse? In what form? For whom? How many times? What sociopolitical lessons should be learned from the past? The different language and storytelling techniques they deploy also urge us ...
Neural-based control of a robotic hand

The neural-based control of a robotic hand has many clinical and engineering applications. Current approaches to this problem have been limited due to a lack of understanding of the relationship between neural signals and dynamic finger movements. Here, we present a technique to predict index finger joint angles from neural signals recorded from the associated muscles. The neural signals are converted to a torque estimate (EBTE) and then input to artificial neural networks. The networks predict the finger position more closely when the input to the networks are torque estimates rather than neural signals. Furthermore, the networks trained with the EBTE signals could predict the joint angles for different phases of finger movements (i.e. dynamic reaching and positioning task) while networks trained with the neural signals could not. Our results indicate that (1) similar finger movements are executed with different synergistic strategies and (2) different phases of finger movements employ different neural strategies. Through these results, we have demonstrated the first concrete technique to control a hand prosthetic device or dexterous tele-manipulator using natural neural control signals. Keywords-motor control, electromyography, joint angles
Development of a Web-Based Psychosocial Intervention for Adolescent and Young Adult Survivors of Pediatric Brain Tumor.

Purpose: To develop A Survivor's Journey, a web-based psychosocial intervention for adolescent and young adult (AYA) survivors of pediatric brain tumors (PBTs). Methods: Stages of development included focus groups with five AYA survivors (ages 16–23 years) and six parents to identify needs and challenges, as well as surveys and interviews with clinical care providers at a survivorship clinic. Results: Concerns reported by AYA survivors, parents, and providers were similar to those reported in the literature, including fatigue, memory deficits, poor mood, health concerns, and challenging peer relationships. However, concerns varied across survivors, underscoring the need for customizable interventions. Survivors and parents were interested in an intervention targeting psychosocial functioning and late effects, and reported a strong preference for web-based interventions that would reduce cost and travel burden on the family. Intervention: Based on review of the literature, survivor and parent feedback, as ...
Structure and Stress Evolution Due to Medium Energy Ion Bombardment of Silicon

Sputtering, stress evolution and surface evolution due to ion bombardment of silicon are studied in this work. Impacts due to argon ions at normal incidence with beam energies of 500eV and 700eV are simulated using Molecular Dynamics (MD). Impacts on (001) silicon surface are simulated on a silicon crystal that is initially undamaged and is 5.43nm × 5.43nm ×5.43nm in dimension. The (001) silicon surface is tiled in order to impose periodic boundary conditions during the MD simulation. Converged statistical description of observables is obtained by performing multiple randomized simulations, with each randomized simulation involving more than 100 ion impacts. A planar radial distribution function and a structure factor-like crystallinity measure are used to study the structure and damage evolution. Stresses are calculated using a force balance method and approach 1.7GPa and 1.3GPa in the 700eV and 500eV cases respectively after about 125 impacts. Continuum descriptions of the damaged surface are obtained from atomistic coordinate data using a silicon probe atom method.
Medicolegal Aspects of the Care of Older Adults

Upon completion of the chapter, the student will be able to: 1. Understand the concept of informed consent. 2. Enumerate the components of an informed consent. 3. Appreciate the importance of advance care planning. 4. Differentiate between competency and decision-making capacity and describe the steps in assessing these in older adults.