cssi/SciSciGPT-SciSciNet huggingface dataset:
Abstract 2473: Fragment-based discovery of inhibitors of replication protein A protein-protein interactions.

Proceedings: AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DC Replication Protein A (RPA) is a heterotrimeric protein that binds to and protects ssDNA and plays an integral role in initiating the cellular response to DNA damage. This response is mediated via protein-protein interactions between a basic cleft on the RPA70N subunit and a number of protein partners, including ATRIP, Rad9, Mre11, and p53. RNAi against RPA has shown an expected toxicity against cancer cell lines, possibly due to abrogation of the ssDNA binding function of RPA. Specific disruption of the protein-protein interactions between the RPA07N subunit and its binding partners has the potential to produce a more selective cytotoxic response in cancer cells. To more accurately dissect the therapeutic relevance of disrupting only the protein-protein interaction functions of RPA, we sought to discover potent small molecule probes that bind to the basic cleft of RPA70N. Inhibition of protein-protein interactions is considered a difficult task. An NMR-based fragment screen has identified more than 130 fragment molecules that bind to the RPA70N protein-protein interaction cleft with affinities that range from 500 μM to 2 mM and corresponding ligand efficiencies from 0.18 to 0.30. Selected fragments, representing several distinct chemotypes, have been optimized for binding to the protein. Using X-ray crystallography, the binding modes of these fragments have been defined. Fragments were found to bind primarily to two main sites within the basic cleft of RPA70N. Additional structure-guided optimizations have been carried out and ternary co-crystal structures have been generated to guide fragment linking strategies. Together, these activities have led to the creation of multiple lead series of inhibitors of the RPA:ATRIP interaction, with binding affinities improved by several fold over the initial fragments. The SAR and biological activities of the fragments and lead compounds will be discussed. Citation Format: Alex G. Waterson, James D. Patrone, J. Phillip Kennedy, Nicholas F. Pelz, Andreas O. Frank, Bhavatarini Vandgamudi, Michael D. Feldkamp, Elaine M. Souza-Fagundes, Olivia W. Rossanese, Walter J. Chazin, Stephen W. Fesik. Fragment-based discovery of inhibitors of replication protein A protein-protein interactions. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2473. doi:10.1158/1538-7445.AM2013-2473
Mapping the zinc transporting system in mammary cells: Molecular analysis reveals a phenotype-dependent zinc transporting network during lactation

The mammary epithelial cell transitions from a non-secreting to a terminally differentiated, secreting cell during lactation. Zinc (Zn) is a key modulator of phenotypic transition as it regulates over 300 biological functions including transcription, translation, energy transformation, intracellular signaling, and apoptosis. In addition, Zn must be redirected from normal cellular functions into the secretory compartment, as many components of the secretory system are Zn-dependent and an extraordinary amount of Zn is secreted (1-3 mg Zn/day) into milk. Herein, we utilized a "systems biology" approach of genomic and proteomic profiling to explore mechanisms through which Zn is reallocated during phenotype transition in the lactating mammary gland from mice and cultured mammary cells. Nine Zn transporters play key roles in Zn redistribution within the network during lactation. Protein abundance of six Zip (Zip3, Zip5, Zip7, Zip8, Zip10, Zip11) and three ZnT (ZnT2, ZnT4, ZnT9) proteins was expanded >2-fold during lactation, which was not necessarily reflected by changes in mRNA expression. Our data suggest that Zip5, Zip8, and Zip10 may be key to Zn acquisition from maternal circulation, while multiple Zip proteins reuptake Zn from milk. Confocal microscopy of cultured mammary cells identified the Golgi apparatus (modulated in part by ZnT5, Zip7, and Zip11) and the late endosomal compartment (modulated in part by ZnT2 and Zip3) as key intracellular compartments through which Zn is reallocated during lactation. These results provide an important framework for understanding the "Zn-transporting network" through which mammary gland Zn pools are redistributed and secreted into milk.
Estimation of the regional cerebral metabolic rate of oxygen consumption with proton detected 17O MRI during precision 17O2 inhalation in swine.

Abstract Despite the importance of metabolic disturbances in many diseases, there are currently no clinically used methods for the detection of oxidative metabolism in vivo . To address this deficiency, 17 O MRI techniques are scaled from small animals to swine as a large animal model of human inhalation and circulation. The hemispheric cerebral metabolic rate of oxygen consumption (CMRO 2 ) is estimated in swine by detection of metabolically produced H 2 17 O by rapid T 1ρ -weighted proton magnetic resonance imaging on a 1.5 T clinical scanner. The 17 O is delivered as oxygen gas by a custom, minimal-loss, precision delivery breathing circuit and converted to H 2 17 O by oxidative metabolism. A model for gas arterial input is presented for the deeply breathing large animal. The arterial input function for recirculation of metabolic water is measured by arterial blood sampling and high field 17 O spectroscopy. It is found that minimal metabolic water “wash-in” occurs before 60 s. A high temporal resolution pulse sequence is employed to measure CMRO 2 during those 60 s after delivery begins. Only about one tidal volume of 17 O enriched oxygen gas is used per measurement. Proton measurements of signal change due to metabolically produced water are correlated with 17 O in vivo spectroscopy. Using these techniques, the hemispheric CMRO 2 in swine is estimated to be 1.23 ± .26 μmol/g/min, consistent with existing literature values. All of the technology used to perform these CMRO 2 estimates can easily be adapted to clinical MR scanners, and it is hoped that this work will lead to future studies of human disease.
Regional cerebral glucose utilization during insulin-induced hypoglycemia in unanesthetized rats.

: Regional cerebral glucose utilization (rCMRgl) was studied during insulin-induced hypoglycemia in unanesthetized rats. Rats were surgically prepared using halothane and nitrous oxide anesthesia and allowed 5 h to recover from the anesthesia before rCMRgl was measured. The rCMRgl was measured using [6-14C]glucose in a normoglycemic control group and two hypoglycemic groups, A (30 min after insulin injection) and B (2 h after insulin injection). The mean plasma glucose level was 7.03 μmol/ml in the normoglycemic group, 1.96 μmol/ml in hypoglycemic group A, and 1.40 μmol/ml in hypoglycemic group B. The rCMRgl in hypoglycemic group A decreased 8–18% in 17 brain regions measured; five changes were statistically significant. The rCMRgl in hypoglycemic group B decreased significantly in all but one of the brain regions measured; the decrease ranged from 15% in the pyramidal tract to 36% in the motor and auditory cortices. The rCMRgl in every brain region decreased when the plasma glucose level fell below 1.5–2.5 μmol/ml. No brain region could maintain rCMRgl at plasma glucose concentrations lower than predicted by regional glucose influx described in previous studies. Glucose utilization in all brain regions appears to be limited by the influx of glucose.
A Holistic Approach for Managing Spyware

Abstract In the past, the main anti-malware targets for IT were viruses and worms. Yet, information privacy and security control are being increasingly challenged by the mushrooming emergence and propagation of spyware, which is one of the perilous cyber-threats confronting the IT community in terms of privacy violation. In general, most people regard spyware as a stealthy transmitter gathering and passing sensitive personal information to a third party over the Internet without awareness or permission. Stafford and Urbaczewski refer to spy- ware as “a ghost in the machine” [1] due to its surreptitious nature compared to viruses and worms. Warkentin et al. [2] further expand the description by arguing that “spy- ware is a client-side software component that monitors the use of client activity and sends the collected data to a remote machine.” The rapid penetration of broadband Internet connections, coupled with a wide variety of free software downloads and weakly managed peer-to-peer (P2P) transmissions, ...
Estradiol replacement in ovariectomized rats increases the hepatic concentration and biliary secretion of α-tocopherol and polyunsaturated fatty acids

Abstract Previously, we showed that estradiol replacement in ovariectomized rats produced prominent increases in serum and liver α-tocopherol (αTP). The present study was conducted to examine whether the estrogen-induced increase in the liver concentrations of αTP affects its biliary secretion and the fatty acid compositions of hepatic and biliary lipids. Ten ovariectomized rats were assigned to two groups: five rats were implanted subcutaneously with time-release estradiol pellets (OXE; 25 μg/day/rat) and five with placebo (OXP). Twice daily rats were pair-fed a modified AIN-93G diet containing soybean oil. At 5 weeks, bile was collected via a bile cannula hourly for 8 hours during duodenal infusion of a lipid emulsion (565 μmol triolein and 396 μmol Na-taurocholate/24 mL phosphate buffered saline, pH 6.45) at 3.0 mL/hr. During the 8-hour period, no difference was noted in the hourly rate of bile flow (0.95 mL/hr in OXE rats vs. 0.99 mL/hr in OXP rats). The biliary output of αTP for 8 hours was higher in OXE rats (51.6 ± 3.6 nmol) than OXP rats (31.7 ± 2.9 nmol). Likewise, the liver concentration of αTP was higher in OXE rats (81.9 ± 3.5 nmol/g liver) than in OXP rats (53.3 ± 7.4 nmol/g liver). The biliary secretion of phospholipids (PL) for 8 hours was significantly ( P
A comparison of hardware implementations of the biorthogonal 9/7 DWT: convolution versus lifting

The filter bank approach for computing the discrete wavelet transform (DWT), which we call the convolution method, can employ either a nonpolyphase or polyphase structure. This work compares filter banks with an alternative polyphase structure for calculating the DWT-the lifting method. We look at the traditional lifting structure and a recently proposed "flipping" structure for implementing lifting. All filter bank structures are implemented on an Altera field-programmable gate array. The quantization of the coefficients (for implementation in fixed-point hardware) plays a crucial role in the performance of all structures, affecting both image compression quality and hardware metrics. We design several quantization methods and compare the best design for each approach: the nonpolyphase filter bank, the polyphase filter bank, the lifting and flipping structures. The results indicate that for the same image compression performance, the flipping structure gives the smallest and fastest, low-power hardware.
Durkheim and Law: Divided Readings over Division of Labor

Recent scholarship on Durkheim draws attention to debates implicating his ideas about law, mainly in The Division of Labor in Society, but also in Professional Ethics and Civic Morals. Division is the better known work, and established readings—otherwise diverse—find in it a thesis about law as the expression of the collective conscience and functioning to maintain community norms. Durkheim's attention to the state in Civic Morals is often read as a continuation of that thesis on law, as if the state were the culmination of collective consciousness. This article reads these works differently, highlighting the discontinuity of states and collective consciousness as the opening for Durkheim's concerns with the moral legitimacy of public authority as well as his efforts to find a subject (literally and figuratively) for the emergent discipline of sociology. The article suggests that current events offer fresh terrain for sociolegal scholars to pursue the implications of Durkheim's insights on law and states,...
Identifying atypical cortisol patterns in young children: The benefits of group-based trajectory modeling

Summary The introduction of growth curve modeling into the ﬁeld of neuroendocrinology hasenabled researchers to examine mean patterns of change in unbalanced and/or incompleterepeated measures data. However, growth curve modeling assumes population homogeneity,orthat all individuals follow roughly the same pattern of change, with differences expressed asdeviation around the mean curve. Group-based trajectory modeling, in contrast, is designed forheterogeneouspopulationsandasaresultisabletoidentifyatypicalpatternsofchangeovertimethatmayexistwithinapopulation.Toillustratethestrengthsandweaknessesofeachtechnique,we apply both to a sample of diurnal cortisol data measured at home in young children (N = 106,46 male, M age = 3.81 years, S.D. = 0.24). We ﬁnd three distinct trajectories of cortisol anddemonstratethatthemembersofthesetrajectoriesaremeasurablydifferentintermsofcortisollevels across context and time and in terms of the relationship between behavioral problems andparenting. At the same time, our growth curve analysis ﬁnds differential response patterns forhigh vs. low internalizing children with high vs. low parenting quality. We discuss these results interms of their implications for the proper application of each method.# 2008 Elsevier Ltd. All rights reserved.* Correspondingauthor.Tel.:+16126242846;fax:+16126246373.E-mail address: gunnar@umn.edu (M.R. Gunnar).available at www.sciencedirect.comjournal homepage: www.elsevier.com/locate/psyneuen0306-4530/$ — see front matter # 2008 Elsevier Ltd. All rights reserved.doi:10.1016/j.psyneuen.2008.08.014
Energy analyses and the determination of multiregional prices

In the last decade, many analysts have tried to investigate energy supplies, demands, and distribution. Most of the studies in the United States have been conducted using a partial equilibrium framework and have concentrated on national supplies, demands, and distribution. In this paper, a theoretical general equilibrium framework is set forth that can be used to trace both the regional and industrial repercussions of changes in wages, prices, or demands in the energy industries. An example of the type of some of the empirical results that are obtainable is also given. Between 1972 and 1976 the price of coal in New England rose from $0.50 per million Btu to $1.26, and the price of oil rose from $0.56 to $1.87. Such increases are very large compared with the usual changes in industrial prices and have led to growing concern over possible repercussions on other industrial prices, on private and public expenditures, and on output and employment. Of particular concern in the present study are the differential regional impacts caused by changes in regional energy costs. The purpose of this paper is to outline a comprehensive and systematic multiregional theoretical framework that can be used to study regional price changes. A primal version of the multiregional input-output (MRIO) model was used in 11974 to analyze the interactions between energy and transportation (Polenske [10]). As far as is known, only two other versions of the MRIO model are being developed at the present time for use in energy analyses. One is the model by Park and Sandoval [9], the other a model by Goettle, Cherniavsky, and Tessmer [5]. Both models are developed for the primal version of the MRIO model, within a linear programming framework. For the present study, a dual version of the MRIO model has been developed. 1 It is an extension of the national price models that have been described by LeonThe author is associate professor of Regional Planning in the Department Of Urban Studies and Planning, Massachusetts Institute of Technology. She acknowledges with gratitude the valuable assistance received from Nathaniel Ng, Ananna S. Tse, and William H. Crown. The data for the multiregional input-output accounting system for 19 industries and 9 regions used for this study were constructed by Nathaniel Ng and Ananna Tse. The calculations for this paper were made by William H. Crown. 1 The theoretical work on various multiregional dual price models was done as a team effort by members of the MRIO research staff. Members participating with the author in this work since 1976 were: Patrick Del Duca, Gary Kaitz, Gregory Pai, Ananna Tse, and Jeffrey Young. Several studies using the dual MRIO system are in progress--Del Duca [3], Pai [8], Young [11].
Examination of the role of the clamp-loader and ATP hydrolysis in the formation of the bacteriophage T4 polymerase holoenzyme

Transient kinetic analyses further support the role of the clamp-loader in bacteriophage T4 as a catalyst which loads the clamp onto DNA through the sequential hydrolysis of two molecules of ATP before and after addition of DNA. Additional rapid-quench and pulse-chase experiments have documented this stoichiometry. The events of ATP hydrolysis have been related to the opening/closing of the clamp protein through fluorescence resonance energy transfer (FRET). In the absence of a hydrolysable form of ATP, the distance across the subunit interface of the clamp does not increase as measured by intramolecular FRET, suggesting gp45 cannot be loaded onto DNA. Therefore, ATP hydrolysis by the clamp-loader appears to open the clamp wide enough to encircle DNA easily. Two additional molecules of ATP then are hydrolyzed to close the clamp onto DNA. The presence of an intermolecular FRET signal indicated that the dissociation of the clamp-loader from this complex occurred after guiding the polymerase onto the correct face of the clamp bound to DNA. The final holoenzyme complex consists of the clamp, DNA, and the polymerase. Although this sequential assembly mechanism can be generally applied to most other replication systems studied to date, the specifics of ATP utilization seem to vary across replication systems.
Design of self-Biased, wideband microstrip circulators for integrated antenna systems

The integration of microwave components into a radar antenna system to achieve high performance, low cost, light weight and compact size is of considerable importance to commercial and military applications [1]. One such component, namely the circulator, is difficult to integrate into such systems due to the specialized materials required (i.e. ferrite) and the need of external biasing magnets, the latter of which is responsible for placing the ferrite in a satura-ed state. In an effort to remove these bulky external magnets, so called ldquoself-biasedrdquo ferrites are a topic of current research. In this work we present a design methodology in which self-biased ferrites can be used in microstrip circulators. This methodology relates the effect of coercivity to bounds on the ferrite geometry, which is not typically done in traditional designs. Using these bounds, we employ a multiple stage parameter search to produce a broadband microstrip circulator design with a 10.7% bandwidth, as validated by simulation.
Internalized Heterosexism Clinical Implications and Training Considerations

This article focuses on implications of empirical research on the construct of internalized heterosexism (IH) in lesbian, gay, and bisexual (LGB) individuals. First, suggestions for practice with LGB clients are provided using the framework proposed by Goodman et al. for social justice work at micro, meso, and macro levels. Second, ideas for the training of counseling psychologists on the construct of IH are presented. Ways in which counseling psychologists can train students beyond the traditional micro-level approach are included.
Highly specific role of the insulin receptor in breast cancer progression

Accumulating evidence from clinical trials indicates that specific targeting of the IGF1 receptor (IGF1R) is not efficient as an anti-breast cancer treatment. One possible reason is that the mitogenic signals from the insulin receptor (IR) can be processed independently or as compensation to inhibition of the IGF1R. In this study, we highlight the role of the IR in mediating breast tumor progression in both WT mice and a hyperinsulinemic MKR mouse model by induction of Ir (Insr) or Igf1r knockdown (KD) in the mammary carcinoma Mvt-1 cell line. By using the specific IR antagonist-S961, we demonstrated that Igf1r-KD induces elevated responses by the IR to IGF1. On the other hand, Ir-KD cells generated significantly smaller tumors in the mammary fat pads of both WT and MKR mice, as opposed to control cells, whereas the Igf1r-KD cells did not. The tumorigenic effects of insulin on the Mvt-1 cells were also demonstrated using microarray analysis, which indicates alteration of genes and signaling pathways involved in proliferation, the cell cycle, and apoptosis following insulin stimulation. In addition, the correlation between IR and the potential prognostic marker for aggressive breast cancer, CD24, was examined in the Ir-KD cells. Fluorescence-activated cell sorting (FACS) analysis revealed more than 60% reduction in CD24 expression in the Ir-KD cells when compared with the control cells. Our results also indicate that CD24-expressing cells can restore, at least in part, the tumorigenic capacity of Ir-KD cells. Taken together, our results highlight the mitogenic role of the IR in mammary tumor progression with a direct link to CD24 expression.
Dual benefit of reduced Cx43 on atherosclerosis in LDL receptor-deficient mice.

Paracrine cell-to-cell interactions are crucial events during atherogenesis, however, little is known on the role of gap junctional communication during this process. We recently demonstrated increased expression of Cx43 in intimal smooth muscle cells and in a subset of endothelial cells covering the shoulder of atherosclerotic plaques. The purpose of this study was to examine the role of Cx43 in the development of atherosclerosis in vivo. Atherosclerosis-susceptible LDL receptor-deficient (LDLR−/−) mice were intercrossed with mice heterozygous for Cx43 (Cx43+/−mice). Male mice with normal (Cx43+/+LDLR−/−) or reduced (Cx43+/−LDLR−/−) Cx43 level of 10 weeks old were fed a cholesterol-rich diet (1.25%) for 14 weeks. Both groups of mice showed similar increases in serum lipids and body weight. Interestingly, the progression of atherosclerosis was reduced by 50% (P < 0.01) in the thoraco-abdominal aorta and in the aortic roots of Cx43+/−LDLR−/−mice compared with Cx43+/+LDLR−/−littermate controls. In addition,...
Genetic assays to define and characterize protein-protein interactions involved in gene regulation.

Abstract Transcription can be regulated during initiation, elongation, and termination by an enormous variety of regulatory factors. A critical step in obtaining a mechanistic understanding of regulatory factor function is the determination of whether the regulatory factor exerts its effect through direct contact with the transcription machinery. Here I describe the application of a transcription activation-based bacterial two-hybrid assay that is useful for the identification and genetic dissection of protein–protein interactions involved in gene regulation. I provide examples of how this two-hybrid system can be adapted for the study of “global” regulatory factors, sequence-specific DNA-binding proteins, and interactions that occur between two subunits of RNA polymerase (RNAP). These assays facilitate the isolation and characterization of informative amino acid substitutions within both regulatory factors and RNAP. Furthermore, these assays often enable the study of substitutions in essential domains of RNAP that would be lethal in their natural context.
A Primary Care Perspective on Gout

Gout causes patientssignificant morbidity, work-related disability, loss of productivity, increased health care costs, and even all-cause hospital admissions. As a result, primary care providers must be armed with the knowledge to properly diagnose and manage gout. While many aspects of care remain the same, some key updates that primary care providers must consider when treating their patients with gout will be discussed. In this perspective we will highlight and discuss acceptable circumstances for empiric treatment, renewed emphasis on treat to target, access to commonly used medications, recommended first line agents, and the role of primary care physicians in gout flare prevention among other topics. These strategies will aid primary care physicians treat all but the most complex cases of gout.
Experimental progress and status on nucleon electromagnetic form factors

Nucleon electromagnetic form factors are the fundamental quantities that are related to a two-dimensional view of the charge and magnetization distribution in the nucleon. They are essential in understanding the nucleon electromagnetic structure. In this article, we briefly summarize the recent experimental progress on this topic, and introduce several experiments related to the nucleon electromagnetic form factors in the near future.
Within-session changes in operant responding when gerbils (Meriones unguiculatus) serve as subjects

Recent research has demonstrated that rate of responding frequently changes in a robust and systematic manner during experimental sessions in which organisms engage in operant responding. One potential cause for these changes in response rate is that levels of exploration change during experimental sessions and that high levels of exploration interfere with operant responding. Several studies have shown that gerbils (Meriones unguiculatus) explore at a constant rate during experimental sessions. The present study examined the response pattern produced by gerbils responding for food delivered by several simple schedules of reinforcement. Results indicated that robust changes (between 200 and 400%) in response rate occurred during the experimental sessions. These data argue against a role for exploration in the production of within-session changes in operant response rate.
Does State Legislation Improve Nursing Workforce Diversity

A health-care workforce representative of our nation's diversity is a health and research priority. Although racial and ethnic minorities represent 37% of Americans, they comprise only 16% of the nursing workforce. The purpose of this study was to examine the effect of state legislation on minority recruitment to nursing. Using data from the National Conference of State Legislatures, American Association of Colleges of Nursing, and U.S. census, we compared minority enrollment in baccalaureate nursing programs of states (Texas, Virginia, Michigan, California, Florida, Connecticut, and Arkansas) before and 3 years after enacting legislation with geographically adjacent states without legislation. Data were analyzed using descriptive and chi-square statistics. Following legislation, Arkansas (13.8%-24.5%), California (3.3%-5.4%), and Michigan (8.0%-10.0%) significantly increased enrollment of Blacks, and Florida (11.8%-15.4%) and Texas (11.2%-13.9%) significantly increased enrollment of Hispanic baccalaureate nursing students. States that tied legislation to funding, encouragement, and reimbursement had larger enrollment gains and greater minority representation.
Cell-balancing currents in parallel strings of a battery system

Abstract Lithium-ion batteries are attractive for vehicle electrification or grid modernization applications. In these applications, battery packs are required to have multiple-cell configurations and battery management system to operate properly and safely. Here, a useful equivalent circuit model was developed to simulate the spontaneous transient balancing currents among parallel strings in a battery system. The simulation results were validated with experimental data to illustrate the accuracy and validity of the model predictions. Understanding the transient behavior of such cell and string balancing in a parallel circuit configuration is very important to assess the impacts of current fluctuation and cell variability on a battery system's performance, regarding durability, reliability, safety, abuse tolerance and failure prevention, including possible short circuit or open circuit conditions. Additional features and advantages, including the ability to assessing impacts on the performance of the string assemblies from string swapping or cell/module replacement in the strings, could be realized to aid battery management, maintenance and repair.
Threshold-linear versus linear-linear analysis of birth weight and calving ease using an animal model: I. Variance component estimation.

Birth weight and calving difficulty were analyzed with Bayesian methodology using univariate linear models, a bivariate linear model, a threshold model for calving difficulty, and a joint threshold-linear model using a probit approach. Field data included 26,006 records of Gelbvieh cattle. Simulated populations were generated using parameters estimated from the field data. The Gibbs sampler was used to obtain estimates of the marginal posterior mean and standard deviation of the (co)variance components, heritabilities, and correlations. In the univariate analyses, the posterior mean of direct heritability for calving difficulty was .23 with the threshold model and .18 with the linear model. Maternal heritabilities were .10 and .08, respectively. In the bivariate analysis, posterior means of direct heritability for calving difficulty were .21 and .18 for the bivariate linear-threshold and linear-linear model, respectively. Maternal heritabilities were .09 and .06, respectively. Direct heritability for birth weight was .25 for the univariate model and .26 for bivariate models. Maternal heritability was .05 for the linear-threshold model and the univariate model and .06 for the bivariate linear model. Genetic correlation between direct genetic effects in both traits was .81 for the linear-threshold model and .79 for the bivariate linear. Residual correlation was .35 for the bivariate linear model and .50 for the bivariate linear-threshold. A simulation study confirmed that the posterior mean of the marginal distribution was suitable as a point estimate for univariate threshold and bivariate linear-threshold models.
The Complexity of Linear Dependence Problems in Vector Spaces.

We study extensions of the k-SUM problem to vector spaces over finite fields. Given a subset S ⊆ Fq of size r ≤ q, an integer k, 2 ≤ k ≤ n, and a vector v ∈ (Fq \ {0}), we define the TARGETSUM problem to be the problem of finding k elements xi1 , . . . , xik ∈ S for which ∑k j=1 vjxij = z, where z may either be an input or a fixed vector. We also study a variant of this, where instead of finding xi1 , . . . , xik ∈ S for which ∑k j=1 vjxij = z, we require that z be in span(xi1 , . . . , xik), which we call the (k, r)-LINDEPENDENCEq problem. These problems are natural generalizations of well-studied problems that occur in coding theory and property testing. Indeed, the (k, r)-LINDEPENDENCEq problem is just the MAXIMUM LIKELIHOOD DECODING problem for linear codes. Also, in the TARGETSUM problem, if instead of general z we require z = 0, then this is the WEIGHT DISTRIBUTION problem for linear codes. In property testing, these problems have been implicitly studied in the context of testing linear-invariant properties. We give nearly optimal bounds for TARGETSUM and (k, r)-LINDEPENDENCEq for every r, k, and constant q. Namely, assuming 3-SAT requires exponential time, we show that any algorithm for these problems must run in min(2, r) time. Moreover, we give deterministic upper bounds that match this complexity, up to constant factors in the exponent. Our lower bound strengthens and simplifies an earlier min(2, r 1/4)) lower bound for both the MAXIMUM LIKELIHOOD DECODING and WEIGHT DISTRIBUTION problems. We also give upper and lower bounds for variants of these problems, e.g., for the problem for which we must find xi1 , . . . , xik for which z ∈ span(xi1 , . . . , xik) but z is not spanned by any proper subset of these vectors, and for the counting version of this problem.
Abstract 1055: CPT1A-mediated lipid catabolism modulates growth, AR expression and hypoxia survival of prostate cancer

Background: Androgen deprivation results in hypoxia in prostate cancer (PCa) cells and subsequently enhances the transcriptional activity of AR leading to more aggressive tumors. Concomitant with hypoxia, a significant accumulation of lipids has been observed but its significance remains unclear. Recent data indicate that lipid oxidation via carnitine palmitoyltransferase (CPT1) results in decreased growth and apoptosis, underscoring the role of lipid as a fuel for PCa growth. Since androgen deprivation ultimately increases the activity of AR, we hypothesized that dual targeting AR and lipid catabolism axes represents an attractive therapeutic approach. Methods: To address the role of lipid use by PCa cells we have used two experimental approaches that lead to lipid accumulation: 1- Use of clinically relevant drugs etomoxir and ranolazine: Etomoxir works by inhibiting CPT1, the rate-limiting step in fat oxidation. Ranolazine is FDA-approved for angina and blocks lipid oxidation in the mitochondria. 2- Hypoxia exposure followed by re-oxygenation to mimic the dynamics of the tumor environment and induce lipid accumulation. Enzalutamide was used by itself or in combination with etomoxir to treat PCa cells, as well as CPT1-edited cells generated in our lab. Drug effects on metabolism and AR expression were studied by growth assays, LCMS, westerns, qRTPCR, and mouse xenograft studies. Results: CPT1 is abundant in androgen-sensitive cells and tumors. Treatment with etomoxir alone significantly decreased cell viability and AR, including the ARv7 variant. Combinatorial treatment with enzalutamide synergistically enhanced this effect on viability. Systemic treatment with ranolazine alone in nude mice bearing enzalutamide-resistant cells resulted in decreased xenograft growth over 21 days, underscoring the therapeutic potential of blocking lipid catabolism to decrease CRPC tumor growth. Lipids accumulated under hypoxia (especially arachidonic acid) were used for growth following re-oxygenation. Pharmacologic inhibition of lipid use or CPT1-knockdown significantly compromised this growth following re-oxygenation, underscoring the role of lipids in supporting aggressive growth. This was observed in sensitive and CRPC models. Conclusions: Lipid accumulation and oxidation is a cyclical phenomenon that modulates AR content and PCa growth. Combination of fat burning inhibitors and enzalutamide may offer a novel approach to anti-AR resistance in PCa, requiring less anti-androgen for more effective therapy. Citation Format: Isabel R. Schlaepfer, Gagan Deep, Rajesh Agarwal, Zhiyong Zhang, Maren Salzmann-Sullivan, Lih-Jen Su, Thomas Flaig. CPT1A-mediated lipid catabolism modulates growth, AR expression and hypoxia survival of prostate cancer. [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 1055.
Representation and incorporation of clinical information in outpatient oncology prognosis using Bayesian networks and Naïve Bayes

Many studies have focused on prognosis for oncology patients with the following characteristics: an inpatient setting (uniform sampling), binary outcomes, and predictor variables of patient demographics and tumor characteristics. This paper examines the problem of predicting prognosis in an outpatient setting (non-uniform sampling), discrete outcomes, and predictor variables of clinical observations. In particular, we consider how to represent the clinical observational data and reason over the prognosis using Bayesian networks (BN) and Naive Bayes (NB). Different representations include trend behaviors using splines and differences over a time period and the clinical observations themselves. The best models were able to outperform the majority classifier with 8.5% (BN) and 10.2% (NB) higher accuracies in predicting a patient's length of survival. The models with highest predictive performance both include a temporal behavioral representation.
Damage Control Resuscitation in Penetrating Trauma: Rules of the Game

Dr. William Halstead once wrote, “The only weapon with which the unconscious patient can immediately retaliate upon the incompetent surgeon is hemorrhage.” In no other field of surgery is this more apparent than in trauma. Hemorrhage is a major factor for mortality in patients presenting after injury. Thus, it is imperative for the competent surgeon to treat hemorrhage expeditiously in order to restore physiologic homeostasis and prevent the dire consequences of ongoing bleeding.
Adjuvant and Neoadjuvant Therapy for Resectable Pancreatic and Periampullary Cancer

Pancreatic adenocarcinoma is a relatively uncommon malignancy associated with a high rate of cancer-related mortality despite best efforts to perform curative surgery. Adjuvant therapy in patients after surgical resection is associated with improved overall survival. Adjuvant treatment approaches may include either chemotherapy alone or a combination of chemotherapy and radiation therapy. Neoadjuvant approaches, also including either chemotherapy alone or a combination of chemotherapy and radiation therapy, are under investigation. Periampullary cancers constitute a rare and heterogeneous group of tumors that are typically treated as pancreatic cancers given their histologic similarities and tumor location.
Brief Announcement: Using Multi-Level Parallelism and 2-3 Cuckoo Filters for Set Intersection Queries and Sparse Boolean Matrix Multiplication

We use multi-level parallelism and a new type of data structures, known as 2-3 cuckoo filters, to answer set intersection queries faster than previous methods, with applications to improved sparse Boolean matrix multiplication.
The new triad power: impact on global markets, resources and politics

Each century has been marked by the successes of different regions and cultures. The trade triad that was prominent in the twentieth and early twenty-first century consisted of Western Europe, North America, and Japan. However, a new triad has been emerging consisting of America, China, and India, and this group will reshape world policy in the twenty-first century. Some of the factors driving this shift in the triad include rapidly aging populations in affluent nations, economic reforms in China and India, and the rise of a new middle class. Unlike the harmony orchestrated by the U.S. in the old triad, the new triad power comes with possible problems, especially between China and the U.S. Their differences will inevitably create tensions, and India will increasingly become a more strategic partner to both. Demand for the world’s resources will create strange bedfellows among nations and resource-driven global expansion for enterprises and nations. Technology breakthroughs will tend to stem from resource conservation and scarcity, shifting the way business around the world is run in the twenty-first century.
Anesthesia for Clavicle Fractures

Clavicle fractures are common, occurring in up to 5% of all fractures and 35% of shoulder girdle fractures [1]. Many of these will require surgical correction and thus also require anesthesia. There are well documented complications associated with clavicle fractures and surgical correction of clavicle fractures [2–4]. Pain from the fracture and from surgical correction can be difficult to manage.
Amifostine reduces gastro-intestinal toxicity after autologous transplantation for multiple myeloma

High-dose melphalan (HDM) followed by autologous hematopoietic cell transplantation (auto-HCT) remains the standard-of-care therapy for multiple myeloma (MM) even with the availability of proteasom...
Controlling for population variances in health and exposure risk using randomized matrix based mathematical modeling

In a previous work, we analyzed the co-occurrence of HPV types in 6 large studies with cervicovaginal samples, representing >32,000 women, to ascertain if associations exist among HPV types and to guide policies on HPV vaccination and vaccine development. The data showed that more women either were uninfected by HPV or had multiple concurrent infections than could be explained by independent assortment, which could result from variance in health and exposure risk factors. Modeling exposure and immune competence proved unstable, so we used a randomized matrix based approach that obviated the need to understand the underlying risk factors. We randomized our source data while preserving increasing levels of fidelity to the original data structures to discover the type associations for HPV infection. We offer that this could be a generally useful technique for studying any type of association in biosocial science, e.g. between demographic, socioeconomic, or other variables.
Cu/Co Multilayer-Based High Signal Integrity and Low RF Loss Conductors for 5G/Millimeter Wave Applications

This paper presents copper/cobalt (Cu/Co) multilayer-based low RF loss conductors and their usage in high signal integrity coplanar waveguide (CPW) transmission lines (TLs) and high Q-factor inductors for the applications of millimeter wave bands including a 28-GHz 5G communication band. Low conductor loss, reduced signal dispersion, and low noise figure of the fabricated devices are featured. CPW (TLs) employing 10 pairs of Cu (150 nm)/Co (25 nm) superlattice conductors, the so-called metaconductors, have been designed and fabricated. Their RF characterization has been performed. Experimental results show a broadband RF resistance reduction of up to 50% (max.) in 7–32 GHz (3.5 Octaves), a phase delay improvement of 25.5%, and a thermal noise voltage reduction of 33% compared to reference Cu-based CPW TLs. In comparison with the devices from the other literature, the presented TLs show the best signal integrity performance in Ku, K, and Ka bands. In addition, a high Q-factor planar inductor on a glass substrate has been designed, fabricated, and characterized as an example of high-performance RF passive components, showing record high Q-factors of 54 at 28 GHz and 63.5 (max.) at 29 GHz.
Chapter VII – Diseases of the Lymph-nodes and Spleen correlated to the Oral Tissues

Publisher Summary This chapter discusses the diseases of the lymph-nodes and spleen correlated to the oral tissues. The lymphatics act universally in oral and systemic diseases. The lymph-nodes of the body are affected by pathologic processes by way of the lymphatics. When chronic infection is present in the body, it spreads to the lymph-nodes and spleen. When localized infection and inflammation are present, they spread to the veins causing compression of veins. As the inflammation spreads through the tissues, it causes dilated lymphatics, except in bone and cartilage. Lymph-nodes commonly respond to pathologic processes by enlargement, that is, Lymphadenopathy. Lymphadenopathy may be because of acute and chronic inflammation, chronic granulomatous inflammation, lymphomas, and metastatic neoplasms. Acute and chronic lymphadenitis are important to the dental practitioner because inflammatory lesions frequently occur in the anterior cervical lymph-nodes because of the infections in the oral cavity. Oral manifestations of the malignant lymphomas are rather rare. Primary malignant lymphomas may develop in the lymphoid tissue in the tonsil, nasopharynx, and rarely in the palate and gingiva. The management of enlarged cervical lymph-nodes is a matter of prime concern to oral surgeons and dental practitioners. If the examining dentist conducts a thorough examination in adult patients, he will generally find that cervical lymphadenopathy is commonly the result of metastases from intra-oral or pharyngeal carcinomas.
Inelastic Modeling and System Identification

Structures under severe loads often go to inelastic range and show nonlinear behavior. Proper modeling of restoring force such that the physical properties can be realistically represented is essential in study of performance and safety of structures under natural or man—made hazards. Also, the estimation of the inelastic structural system parameters and their uncertainties should be based on experimental or field evidence of actual structures, therefore requires methods of system identification and regression analysis. Recent developments in the above areas are summarized with emphasis on restoring force hysteresis, degradation, biaxial interaction and capacity against damage. A simple time domain least—square technique for practical evaluation of restoring force parameters is also presented. Numerical examples are given and applications to damage prediction and damage limiting design are mentioned.
Sleep Disorders: Psychological Aspects

Psychological factors play a role in the etiology, maintenance, and consequences of many of the disorders of sleep. They constitute risk factors for some of the most prevalent disorders in each of the major categories: the insomnias, the hypersomnias, and the parasomnias. Longitudinal studies of insomnia demonstrate that those with persistent poor sleep are at greater risk for new diagnoses of both anxiety and major mood disorders. Similarly poor health habits such as smoking, alcohol abuse, a sedentary life style, and diet leading to obesity, are all risk factors for the major sleep disorder of the hypersomnia group: Obstructive Sleep Apnea syndrome. The excessive daytime sleepiness associated with this diagnosis impacts social role performance, employment, as well as cognitive functioning and emotional well being. Psychological factors have also been implicated in vulnerability to the parasomnias such as post-traumatic stress disorder (PTSD) with its characteristic repetitive nightmares. Prior sleep deprivation and ongoing unresolved emotional stress can also precipitate episodes of the parasomnias of sleepwalking and night terrors in those genetically vulnerable.
The Effects of Temperature, Nutrients, and Spore Concentration on the Germination of Conidia from Dactylomyces thermophilus

Cooney and Emerson (1964) defined thermophilic fungi as those fungi having a minimum temperature for growth at or above 20C and whose maximum temperature for growth is at or above 50C. Thermophiles have been isolated from a wide variety of habitats and contribute to the decomposition of materials such as stored products, municipal wastes, and compost. Recently, Deploey and Gautam (1987), and Deploey (1989) reported results of studies concerning the germination of spores from two thermophilic species of Rhizomucor (R. miehei and R. pusillus). Other studies of the germination of spores from thermophilic and thermotolerant fungi have also been reported (Celerin and Fergus, 1971; Deploey, 1985; Fergus and Delwiche, 1975; Jack and Tansey, 1977; Streets and Ingle, 1972; Sussman, 1976), but of these only one (Jack and Tansey, 1977) concerned the germination of spores from Dactylomyces thermophilus. In their study Jack and Tansey (1977) reported the results of germination studies of D. thermophilus, conidia exposed to sun-heated soil, sun-shaded soil, and at 22–24C and 37C in the laboratory. However, their study of D. thermophilus did not include any other parameters influencing spore germination. Since so little is known concerning the germination of conidia from D. thermophilus, studies were done here to determine the effects of temperature, spore concentration, and nutrients on the germination of these spores.
Large Errors from Assuming Equivalent DC and High-Frequency Electrical Characteristics in Metal–Multiple-Insulator–Metal Diodes

Metal–insulator–metal (MIM) tunnel diodes are essential for ultra-high-speed rectification. We review an erroneous method for distributing DC voltage drops across multiple insulator layers that is used in all the published literature on these devices. It has resulted in large errors between designed and fabricated multi-insulator diodes. For multi-insulator MIM diodes, voltage division is dependent on both tunneling resistances and oxide capacitances. We demonstrate that correct voltage division at DC is determined by the rectification resistance, as opposed to the commonly used capacitive voltage division. We find that DC characteristics of multi-insulator diodes cannot be used to predict high-frequency behavior.