cssi/SciSciGPT-SciSciNet huggingface dataset:
Abstract 3497: SAMHD1 is a Novel Biomarker and Therapeutic Target for Radiation Therapy and PARP Inhibition in Breast Cancer

SAMHD1 is a Novel Biomarker and Therapeutic Target for Radiation Therapy and PARP Inhibition in Breast Cancer Ashley Schlafstein, Waaqo Daddacha, David S. Yu Background/Introduction: Patients with breast cancer are often treated by ionizing radiation (IR) and PARP inhibitors; however, the effectiveness of these treatments is often limited by lack of response and/or resistance. Sterile alpha motif and HD domain-containing protein 1 (SAMHD1) is a deoxyribonucleotide triphosphate (dNTP) triphosphohydrolase with a well-established role in HIV-1 restriction by depleting dNTPs required for reverse transcription and replication. SAMHD1 is also dysregulated in breast and other cancers and in autoimmune disease. In addition to its well-established dNTPase activity, our lab has defined a novel role for SAMHD1 in DNA end resection to facilitate DNA double strand break (DSB) repair by homologous recombination (HR). Because of its role in DNA DSB repair and its link to breast cancer, we hypothesized that SAMHD1 could be used as a novel biomarker and target for breast cancer therapy. Methods: We queried the TCGA database for patients with breast cancer who were treated with or without IR to determine if there was an association of SAMHD1 expression level with clinical outcome. We also determined if targeting SAMHD1 for proteasomal degradation with novel virus like particles (VLPs) containing Vpx, a viral accessory protein, can sensitize breast cancer cells and tumors to DNA damaging agents. Results: In patients with breast cancer treated with IR, low SAMHD1 expression was associated with a statistically significant improvement in overall survival, while for those not treated with IR, no significant difference in association of SAMHD1 expression with outcome was observed. Breast cancer cells and tumors treated with VLPs containing Vpx were hypersensitive to IR and PARP inhibitor. Conclusion: Our results identify SAMHD1 as a novel biomarker for stratifying breast cancer patients for treatment with IR. In addition, targeting SAMHD1 with VLPs containing Vpx may be a novel therapeutic strategy for sensitizing breast cancer to IR, PARP inhibitors, and other agents that induce DNA DSBs. Citation Format: Elizabeth Thompson. SAMHD1 is a Novel Biomarker and Therapeutic Target for Radiation Therapy and PARP Inhibition in Breast Cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3497.
Disruptive Experiences as Tools for Teacher Education: Unearthing the Potential of Experiential Education:

Background: This study examines the role of a weeklong experiential residency program on teachers’ beliefs about self and practice. Purpose: The goal of two separate intensive experiences was to he...
Development of Building Restoration Functions for Use in Community Recovery Planning to Tornadoes

AbstractPostdisaster community scale recovery and resilience assessments have gained interest in the United States and around the world following natural and human-made disasters. Tornadoes are one...
Radiofrequency Ablation for Treating Headache: a Follow-up Study

To identify the efficacy of radiofrequency ablation of pericranial nerves in treating headache. Recent studies by the same group showed promising results in treating headache using radiofrequency ablation. Pericranial nerves can be a therapeutic target for treating headache. Our results showed efficacy of radiofrequency ablation. More studies using other modalities as neuromodulation are needed and may show efficacy as well.
Comparing Constraints on Contraction Using Bayesian Regression Modeling.

This paper has three goals: (1) to document the factors shaping is-contraction in Mainstream American English; (2) to assess the extent to which these factors also shape contraction of 'has'; (3) to use shared patterns of contraction across the two verbs to draw conclusions about how the varying forms are represented grammatically. While 'is' has two distinct phonological forms in variation, 'has' has three. This necessitates regression modeling which can handle non-binary response variables; I use Bayesian Markov chain Monte Carlo modeling. Through this modeling, I (1) uncover a number of novel predictors shaping contraction of 'is', and (2) demonstrate that many of the patterns shown by 'is' are also in evidence for 'has'. I also (3) argue that modeling 'has'-variation as the product of two stages of binary choices --- a common treatment of three-way variation in variationist sociolinguistics --- cannot adequately explain the quantitative patterns, which are only compatible with a grammatical model under which three distinct forms vary with each other. The findings have theoretical and methodological consequences for sociolinguistic work on ternary variables.
Perceptions of Conversational Group Membership based on Robots' Spatial Positioning: Effects of Embodiment

Robots' spatial positioning is a useful communication modality in social interactions. For example, in the context of group conversations, certain types of positioning signal membership to the group interaction. How does robot embodiment influence these perceptions? To investigate this question, we conducted an online study in which participants observed renderings of several robots in a social environment, and judged whether the robots were positioned to take part in a group conversation with other humans in the scene. Our results suggest that robot embodiment can influence perceptions of conversational group membership. An important factor to consider in this regard is whether robot embodiment leads to a discernible orientation for the agent.
The Social Contract and Civil Unrest: The Tenuous Balance Between Freedom and Security

The COVID-19 pandemic has served as an impetus for change in how people and governments both exist and co-exist in the “New Normal.” Civil unrest marked by protests and, in some cases rioting, has been fueled by factors other than COVID-19. These factors are racial discrimination, economic downturn and stagnation, and political oppression. As this chapter will show, each of the four can be linked as a causal variable to the other. Particular attention has been paid to the impact of COVID-19 on the tenets of Social Contract Theory and how the balance of personal freedom and security on the part of the citizen requires change during the time of crisis. This discussion will be framed using recent events in the United States in a case study manner to primarily illustrate COVID-19 influenced protests, but also correlated protests pertaining to racial unrest. The chapter also addresses how other governmental systems have used the pandemic as a mechanism to further their own agendas. It concludes with a discussion of policing and calls for change in the law enforcement mission as they are the most visible and recognizable members of the bureaucratic state.
Conformational analysis—CXXIII: Carboxylic acids and esters in force field calculations

Abstract Force field calculations have been extended to include carboxylic acids and esters. Necessary parameters were chosen mainly by fitting to available experimental data on small molecules. A few key facts are not known experimentally, and these were found by carrying out ab initio (STO-3G) calculations. Other molecules were then studied and structural predictions were made. It is predicted that in isobutyric acid a methyl group is twisted 15° from eclipsing the carbonyl oxygen in the ground state. The relative energies and torsional functions for cyclohexanecarboxylic acid are reported. Except for rather simple compounds, such as normal chains, the carboxyl is usually twisted with respect to the attached chain. Some conformations of lactones were also examined. For δ-valerolactone it is predicted that the boat conformation is more stable than the chair. Heats of formation of the compounds can be calculated with fair accuracy.
Emotional Communities in the Early Middle Ages

Proposing that people lived (and live) in "emotional communities"-each having its own particular norms of emotional valuation and expression-Barbara H. Rosenwein here discusses some instances from the Early Middle Ages. Drawing on extensive microhistorical research, as well as cognitive and social constructionist theories of the emotions, Rosenwein shows that different emotional communities coexisted, that some were dominant at times, and that religious beliefs affected emotional styles even as those styles helped shape religious expression. This highly original book is both a study of emotional discourse in the Early Middle Ages and a contribution to the debates among historians and social scientists about the nature of human emotions. Rosenwein explores the character of emotional communities as discovered in several case studies: the funerary inscriptions of three different Gallic cities; the writings of Pope Gregory the Great; the affective world of two friends, Gregory of Tours and Venantius Fortunatus; the Neustrian court of Clothar II and his heirs; and finally the tumultuous period of the late seventh century. In this essay, the author presents a new way to consider the history of emotions, inviting others to continue and advance the inquiry. For medievalists, early modernists, and historians of the modern world, the book will be of interest for its persuasive critique of Norbert Elias's highly influential notion of the "civilizing process." Rosenwein's notion of emotional communities is one with which all historians and social scientists working on the emotions will need to contend.
Link management in the Air Force airborne network

The envisioned Air Force airborne network (AF AN) circa 2020 will most likely consist of a backbone network and many edge networks. The backbone nodes are expected to experience semi-permanent connectivity whereas the edge network nodes may experience rapidly changing connectivity in an ad-hoc manner. In addition, nodes may join and leave any edge network at fairly rapid rates. In this environment there is a need to manage link connectivity, node membership and the overall network topology in such a way as to minimize the impact of rapidly-changing connectivity and node network membership on the performance of user information transfers. This rapid detection/response management of links, nodes and the overall topology is defined as link management (LM), This paper describes the LM approach being taken for the AF AN circa 2020. The following topics are addressed: (a) high level LM functions from a network perspective, (b) LM architecture alternatives based on the extent of centralization/decentralization employed, and (c) a proposed LM functional allocation between platform and terminal equipment. Finally, this paper identifies sample issues pertaining to the successful development of an AN LM system, along with possible methods to resolve these issues.
Infiltration from a strip source

[1] This study addresses infiltration from strip sources of water on the soil surface. The problem arises as the limiting case of furrow irrigation as well as for closely spaced surface drip emitters. Previously, the most common approach used for describing flow from strip sources was numerical modeling based on Richards' equation. This work investigates a third approach borrowed from previous applications for infiltration from disc sources. The assumption is that when the cumulative infiltration is expressed per unit area of the wetted strip, the difference of that value and one-dimensional infiltration is linear with time. We test the assumption directly by doing numerical experiments with six representative soils and using various strip widths, boundary, and initial water contents. The general conclusions are that the differences between the cumulative infiltration per unit source area for a strip and a planar source are linearly related to time but that a single value of the proportionality factor γ is generally inadequate. Values of γ are found between 0.64 and 1.16. An effort was made to relate γ to soil hydraulic parameters and strip width as well as to the boundary and initial conditions. Once γ is defined, the strip infiltration follows immediately if the corresponding one-dimensional solution is known without the necessity of performing a two-dimensional simulation.
Immune Deficiency Influences Juvenile Social Behavior and Maternal Behavior

Mice with severe combined immunodeficiency (SCID) lack functional T and B lymphocytes, and have impaired cognitive abilities. We assessed social behaviors in male SCID and C57BL/6 (B6) juvenile mice. In a social preference task, SCID mice spent more time than B6 mice investigating a novel adult male mouse. In a social recognition task, SCID mice habituated to a novel ovariectomized mouse, but failed to show dishabituation when presented with an unfamiliar individual. We hypothesized that partial immune restoration could normalize behaviors. SCID pups (postnatal Day 7) received either saline or splenocytes from normal donors. Splenocyte-replaced SCID mice spent less time interacting with a novel mouse than saline-injected SCID or B6 control mice. Again, control SCID mice failed to dishabituate to a novel mouse, but splenocyte-replaced SCID mice showed dishabituation. In both of these studies, B6 and SCID pairs were used to produce offspring that remained with their dams until weaning. There are no studies of maternal behavior in SCID dams; therefore to investigate the potential role for this factor, we quantified maternal behavior in SCID and B6 dams; several significant differences were found. To control for differences in maternal care, we mated heterozygous SCIDs to produce offspring. These homozygous SCID and wild-type offspring reared by dams of the same genotypes displayed similar responses to a novel mouse; however, in the social recognition task, SCID males did not display dishabituation to a novel mouse. Taken together, our data indicate that Gene × Environment interactions influence social interactions in immune deficient mice.
Molecular cloning and expression of a unique receptor-like protein-tyrosine-phosphatase in the leucocyte-common-antigen-related phosphatase family

Protein-tyrosine-phosphatases (PTPases) have been implicated in the regulation of certain tyrosine kinase growth factor receptors in that they dephosphorylate the activated (autophosphorylated) form of the receptors. In order to identify PTPases that potentially act on receptor targets in liver, we used the human leucocyte common antigen-related PTPase (LAR) cDNA [Streuli, Krueger, Hall, Schlossman and Saito (1988) J. Exp. Med. 168, 1523-1530] and isolated two closely related transmembrane PTPase homologues from a rat hepatic cDNA library. Both PTPases had large extracellular domains that contained three immunoglobulin-like repeats and eight type-III fibronectin repeats. Both enzymes had tandem homologous PTPase domains following a single hydrophobic transmembrane domain. One sequence encoded the rat homologue of LAR. The second PTPase, designated LAR-PTP2, had 79 and 90% identity with rat LAR in the respective cytoplasmic PTPase domains, with only 57% sequence similarity in the extracellular domain. The catalytic domains of LAR and LAR-PTP2 prepared by bacterial expression were active in dephosphorylating a variety of phosphotyrosyl substrates but did not hydrolyse phosphoserine or phosphothreonine residues of labelled casein. Both enzymes exhibited rapid turnover numbers of 4-7 s-1 for myelin basic protein and 78-150 s-1 for derivatized lysozyme. LAR and LAR-PTP2 displayed similar PTPase activity towards the simultaneous dephosphorylation of receptors of intact insulin and epidermal growth factor from liver membranes. These data indicate that there is a family of LAR-related PTPases that may regulate the phosphorylation state of receptor tyrosine kinases in liver and other tissues.
Direct Final Rulemaking in the FDA: Lessons from the First Decade

In an effort to improve efficiency, several administrative agencies, including the Food and Drug Administration, have adopted a procedure known as direct final rulemaking (DFR). Some academics have debated whether DFR violates the Administrative Procedure Act, but none have studied how DFR has functioned in practice. This paper, which examines the first decade of DFR at the FDA, is the first of this kind. The results are surprising, and suggest DFR deserves more study than it has received. Intended for noncontroversial rules that are expected to receive no significant comments in a notice-and-comment rulemaking, FDA has often used direct final rulemaking for the opposite: regulations that may be expected to be controversial. Far from generating few comments, forty percent of DFRs have had to be withdrawn due to significant opposition. These findings suggest greater limits be placed on the use of direct final rulemaking and that its legality be re-evaluated in light of how the procedure is actually used.
Bovine herpesvirus type 1 (BHV-1) mutant lacking UL49.5 luminal domain residues 30–32 and cytoplasmic tail residues 80–96 induces more rapid onset of virus neutralizing antibody and cellular immune responses in calves than the wild-type strain Cooper

Bovine herpesvirus type 1 (BHV-1) envelope protein U(L)49.5 inhibits transporter associated with antigen processing (TAP) and down-regulates cell-surface expression of major histocompatibility complex (MHC) class I molecules to promote immune evasion. Earlier, we have constructed a BHV-1U(L)49.5Δ30-32 CT-null virus and determined that in the infected cells, TAP inhibition and MHC-I down regulation properties of the virus are abolished. In this study, we compared the pathogenicity and immune responses in calves infected with BHV-1U(L)49.5Δ30-32 CT-null and BHV-1 wt viruses. Following primary infection, both BHV-1 wt and BHV-1U(L)49.5Δ30-32 CT-null virus replicated in the nasal epithelium with very similar yields. BHV-1 antigen-specific CD8+ T cell proliferation as well as CD8+ T cell cytotoxicity in calves infected with the BHV-1U(L)49.5Δ30-32 CT-null virus peaked by 7 dpi (P<0.05) which is 7 days earlier than that of BHV-1 wt-infected calves. Further, virus neutralizing antibody (VN Ab) titers and IFN-γ producing peripheral blood mononuclear cells (PBMCs) in the U(L)49.5 mutant virus-infected calves, also peaked 7 days (IFN-γ; P<0.05) and 14 days (VN Ab; P<0.05) earlier, respectively. Therefore, relative to wt in the BHV-1U(L)49.5 mutant virus-infected calves, primary neutralizing antibody and cellular immune responses were induced significantly more rapidly.
Nonadiabatic transient behavior of quantum well photodetectors

ABSTRACT In the presence of a time-dependent external source such as a bias electric field, an incident optical flux, or thetemperature, electrons in quantum well devices experience non-adiabatic transport through the barrier layer between twoadjacent quantum wells. This non-adiabatic transport process induces charge density fluctuations within each quantumwell, resulting in several seemingly unrelated transient phenomena. When a time-dependent electric field is applied tothe system, a dynamical breakdown ( i.e., the dark current is dominated by a dielectric displacement current) and a zero-bias residual dark current in the quantum-well photodetectors are predicted theoretically. If a chopped time-dependentoptical flux is incident on the system, a dynamical drop in the photo-responsivity with increasing chopping frequencyand an emission-current spike as the optical shutter is opened are predicted. Finally, as the device temperature is variedwith time, a counter-clockwise thermal hysteresis is found theoretically in the dark current curve as a function of thechanging temperature. Experimental confirmation of the above theoretical predictions is presented.Keywords: QWIP, quantum well detector, infrared detection, dark current, transient behavior
A NOTE ON SPECIFICATION OF CLIMATE VARIABLES IN MODELS OF POPULATION MIGRATION

In the literature on population migration increasing attention has been devoted to quality-of-life factors. Measures of temperature (as proxies for climate) have frequently been employed in empirical work regarding the determinants of population migration decisions. A wide range of such specifications have been used most of which imply restrictions on the preferences of migrants. In this paper a variety of temperature variable specifications are analyzed and interpreted. Statistical tests for nested and nonnested hypotheses are used to compare and choose among the various specifications. The model is used to analyze interstate migration in the 48 contiguous states of the United States for the period 1975-1980. (EXCERPT)
Cost-effectiveness of biologic treatments for psoriasis based on subjective and objective efficacy measures assessed over a 12-week treatment period

Background The cost-effectiveness of biologic agents is not well delineated. Objective To determine the cost-effectiveness of biologic agents in cost per patient achieving a minimally important difference in Dermatology Life Quality Index (DLQI MID) and cost per patient achieving a 75% improvement in Psoriasis Area Severity Index (PASI-75), assessed over a 12-week period. Method Efficacies of the agents were determined through a literature review; treatment paradigms and associated costs were determined. The cost-effectiveness of the agents was determined and sensitivity analysis performed. Results Etanercept at a dose of 25 mg administered subcutaneously (SQ) once weekly was the most cost-effective agent in cost per patient achieving DLQI minimally important difference; infliximab at a dose of 3 mg/kg administered intravenously (IV) for 3 infusions, adalimumab at a dose of 40 mg SQ every other week, and etanercept at a dose of 25 mg SQ twice weekly were the next most cost-effective agents in cost per patient achieving the DLQI minimally important difference. Intravenous infliximab at a dose of 3 mg/kg was the most cost-effective agent in terms of cost per patient achieving PASI-75 improvement; intravenous infliximab at a dose of 5 mg/kg and adalimumab at a dose of 40 mg SQ every other week were the next most cost-effective agents in cost per patient achieving PASI-75 improvement. Limitations This study had a limited time horizon of 12 weeks; generalizing the results to longer treatment periods may not be accurate and is not advisable. Additionally, when sensitivity analyses were performed, multiple agents had overlapping cost-effectiveness ratios at relatively low levels of variance; thus it may not be accurate to differentiate the cost-effectiveness of these agents. Conclusions Different biologic agents for psoriasis appear to have different cost-effectiveness values; within the limitations of the available data, infliximab and adalimumab appear to be the most cost-effective agents.
Isotopic composition of cosmic-ray boron and nitrogen

New measurements of the cosmic-ray boron and nitrogen isotopes at earth and of the elemental abundances of boron, carbon, nitrogen, and oxygen are presented. A region of mutually allowed values for the cosmic-ray nitrogen source ratios is determined, and the cosmic-ray escape mean free path is determined as a function of energy using a leaky box model for cosmic-ray propagation in the Galaxy. Relative to O-16, a N-15 source abundance consistent with solar system composition and a N-14 source abundance which is a factor of about three underabundant relative to the solar value are found.
Functional 3-D magnetic nanostructures

Most of magnetic nano-structures today are ultrathin or nanostructured films and multilayers. The main challenge is to find a suitable technology to integrate and to contact nanostructures in a reliable manner. Here, we investigate the problem of contact integration into functional 3-D devices and evaluate the influence of 3-D magnetic layer geometry on performance of magneto-electronic devices. Real devices are truly 3-dimensional structures. Their topography must absolutely be taken into consideration during the design phase since their inherent non-planarity will profoundly affect their magnetization profile. Our initial results strongly indicate that the “non-flatness” of magnetic layer strongly influences the possible magnetic states, alters the switching mechanism and leads to totally new behavior, which was not observed in classic 2-D thin film magnetic structures.
24 Infant eczema

Abstract PURPOSE: To investigate the development of infant eczema in an ethnically diverse population. Infant feeding practices including age at introduction of solid food and duration of breastfeeding were considered as predictors. METHODS: A cohort of 885 infants, each with an asthmatic sibling, was enrolled in a prospective study within 3 months of birth. Mothers were recontacted when the child was 12 months old and reported the development of eczema, allergy and asthma. Adjusted odds ratios and confidence limits were estimated using logistic regression models. RESULTS: Hispanic children were less likely to develop eczema (12%) than either white (27%) or black (27%) children (OR 0.5 95% CI 0.3, 0.9). However, children whose mothers graduated from college were most likely to develop eczema (33%) and children whose mothers did not complete high school (12%) were least likely (OR 2.5 95% CI 1.2, 5.0). The development of eczema was associated with reactions to solid food (OR 2.1 95% CI 1.3, 3.4) and development of allergies that cause “cold-like” symptoms (OR 1.6 95% CI 1.1, 2.5). Breastfeeding (⩾6 months), age at which formula was first given, and introduction of solid food before 3 months were not associated with eczema, nor were child's gender or maternal or paternal history of allergies or asthma. CONCLUSION: Children of higher socioeconomic status were more likely to develop eczema, but black children had the same risk as whites, while Hispanic children were protected. Breastfeeding did not prevent the development of eczema and introduction of solid food before 3 months was not harmful.
High-performance liquid chromatography of the oligonucleotides

Abstract Improved separations of the protected oligonucleotides are reported using a polar bonded CN phase with gradient elution (methylene chloride-methanol mobile phase). This packing yielded high recoveries, and overcame some of the problems associated with the use of highly polar silica columns. In addition, the application of reversed-phase and ion-pair high-performance liquid chromatography is demonstrated for the oligonucleotides and for the nucleosides and mononucleotides, respectively. Ion-pair chromatography was used to accomplish the simultaneous separation of the ribo- and deoxyribonucleosides and their mononucleotides. A novel method for the determination of oligomer chain length is also reported, using diesterase cleavage and ion-pair high-performance liquid chromatography.
Long-range interatomic dipoles

Interatomic electric dipole moment coefficient derivation by approximation involving accessible atomic properties, noting application to H atoms
Optically pumped NMR: Revealing spin-dependent Landau level transitions in GaAs

We show that high-resolution optically pumped NMR (OPNMR) studies can reveal spin-dependent optical transitions between valence- and conduction-band Landau levels in bulk semiconductors such as GaAs. The OPNMR signal intensity exhibits oscillations as a function of pump photon energy that evolve with magnetic field. In contrast to standard polarized magnetoabsorption measurements, OPNMR is sensitive to the polarization of the photoexcited electron spins (i.e., the difference between spin-up and spin-down electron populations rather than the sum). This allows one to clearly resolve the spin dependence of optical transitions that might normally be obscured in conventional magnetoabsorption studies. The data are in good agreement with theoretical calculations of the transitions from the spin-split light-hole Landau levels in the valence band to the conduction-band Landau levels of GaAs.
Nanofiltration membranes based on thin-film nanofibrous composites

Abstract Thin-film nanofibrous composite (TFNC) membranes, containing a multi-layered structure, for nanofiltration (NF) were demonstrated. The best performing membranes consisted of a three-layered structure, including the poly(ethylene terephthalate) (PET) non-woven support, polyacrylonitrile (PAN) electrospun mid-layer, and composite barrier layer based on cellulose nanofibers (CN) and polyamide (PA) matrix made by interfacial polymerization. Under the chosen test conditions (482 kPa, 2000 ppm MgSO 4 as the feed solution), all manually coated TFNC-NF membranes exhibited high rejections (above 99%), where the best membrane showed a flux of 44.7 L/m 2 h (LMH), significantly higher than that of the membrane prepared by the conventional phase-inversion substrate (its flux was 27.6 LMH). Transmission electron microscopy (TEM) indicated that the CN component embedded in the PA matrix probably introduced directed water channels, thus increasing the permeability of the barrier layer. The machine-driven slot-die coating method was applied to improve the membrane performance by reducing the barrier layer thickness through regulating the organic solution delivery in interfacial polymerization. With the optimized organic solution delivery, the membranes exhibited a flux of 71.7 LMH and a rejection of 98.5%, which were better than those of a commercial NF membrane (DOW Filmtec NF 270) having similar barrier layer chemical compositions. The flux of the slot-die coated TFNC-NF membrane was further improved by using 20 wt% bipiperidine (BP) with respect to the total amine monomers for interfacial polymerization, where the membrane exhibited a flux of 94.3 LMH (i.e., doubling the flux of NF 270) and a rejection of 96.7% (the rejection of NF 270 was 97%).
Calibrating Urban Residential Location Models 3: Empirical Results for Non-US Cities

This paper is the third in a series describing extensive empirical verification (by parameter estimation) of the Disaggregated Residential Allocation Model (DRAM). The first paper in this series, Putman and Ducca (1978a), described procedures for estimating the parameters of this type of model when trip interchange (O-D trip matrices) are unavailable. The second paper in this series, Putman and Ducca (1978b), described the results of estimating parameters in this way for a dozen US cities. This paper continues the work with parameter estimation for more than a dozen disparate non-US cities. The results lend even greater confirmation of the descriptive validity of this type of model.
Dual actions of guanethidine on amine uptake mechanisms in adrenergic neurons.

Abstract By using a technique which allows the differentiation in vitro between amine uptake mechanisms in adrenergic neurons, evidence is presented that guanethidine at 10 −4 M inhibits both a membrane amine pump and an intracellular amine-concentrating mechanism. At a low concentration of guanethidine (5 × 10 −6 M) the intracellular mechanism is preferentially inhibited. The action of guanethidine on the membrane pump is readily removed by washing. It is concluded that at clinical doses, guanethidine acts only on the intracellular mechanism, thus leading to depletion of norepinephrine.
Adapting Server Systems for New Memory Technologies

After decades of a cache, DRAM, and disk data storage hierarchy, new memory technologies are promising nonvolatility, high endurance, and fine-grained data access--all of which could, with some preparation, enable a new storage paradigm in server systems.
Conditioned place aversion induced by intragastric administration of ethanol in rats

Most experiments investigating ethanol-induced place conditioning in rats have produced conditioned place aversion (CPA). In one of the few reports of ethanol-induced conditioned place preference (CPP) in rats, selectively bred alcohol-preferring (msP) rats showed CPP in a biased procedure when ethanol was administered via intragastric (IG) catheter but not when ethanol was administered via intraperitoneal injection or by gavage. This finding suggests the importance of both route of administration and genetic variables to the outcome of place conditioning studies. We conducted three experiments examining place conditioning induced by IG ethanol in genetically heterogeneous rats to test the generality of the earlier finding. We employed an unbiased procedure that is more sensitive to detecting preference changes in either direction (preference or aversion). Ethanol-naive (Experiment 1) and ethanol-experienced Sprague-Dawley rats (Experiment 2) showed robust CPA. In Experiment 3, infusion rate was varied to see if the CPA observed in Experiments 1 and 2 was a result of the rapidity of the transition from the sober to the intoxicated states. Both groups showed strong CPA. Overall, the present findings are consistent with previous findings of CPA in heterogeneous rats, suggesting that the aversive postabsorptive effects of ethanol produce CPA.
Phototherapy of jaundice in newborn infants. I. ABO blood group incompatibility

A controlled study of phototherapy was carried out in 35 infants with neonatal hyperbilirubinemia due to maternal-fetal ABO blood group incompatibility. Sixteen of the subjects weighed less than 2,500 Gm. at birth, and 19 weighed 2,500 Gm. or more. Phototherapy caused a marked decline of serum bilirubin concentration at a time when such levels were rising in the control infants and prevented mean peak bilirubin concentrations in the treated infants from reaching the levels attained by the control infants. No treated infants required exchange transfusion, but 5 of the control infants did. The heavier skin pigmentation in Negro subjects did not reduce the effectiveness of phototherapy.
Elastic constants of a Si/Ge superlattice and of bulk Si and Ge.

We report extensive convergence tests of the total energy of Si computed within the local-density approximation with a plane-wave basis and pseudopotentials. These convergence tests indicate that to calculate the elastic constants to about 3% relative error requires the use of 400 plane waves in the electronic structure calculation and 10 special k points to compute the density and energy. Further, we find that using the Ceperley-Alder exchange-correlation form in calculating the elastic constants obtains better agreement with the experimental results than using the Wigner form. We report the calculated lattice constants and elastic constants---bulk modulus, ${\mathit{C}}_{11}$, ${\mathit{C}}_{12}$, and ${\mathit{C}}_{44\mathrm{---}}$of a ``free-standing'' Si/Ge ordered superlattice. For comparison, the results for bulk silicon and germanium are in excellent agreement with existing experiment and other calculations. The calculation for ${\mathit{C}}_{44}$ reported here is unique in the sense that the ``internal'' atom in the diamond unit cell moves while the crystal is sheared, though previously this relaxation has been dealt with differently. The equilibrium position of the sheared crystal cannot be predicted by scaling arguments from the unstrained crystal. An ``averaged elastic theory'' based on bulk Si and bulk Ge predicts our computed Si/Ge lattice constant and bulk modulus surprisingly well.
The study of soil chemistry through quasi-steady-state models: I. Mathematical definition of model

Abstract A mathematical method for studying the composition and speciation of soil solutions is presented. The method is formulated in general algebraic terms, and is adaptable to soil-water systems of virtually any chemical composition. Chemical processes in three different time frames are considered: fast, reversible processes, described in terms of chemical equilibrium; slow processes, described by kinetic equations for which the steady-state solution is found; and very slow processes, which are considered to be invariant in time for the solution of the system. The rates of the slow processes are written as functions of concentrations of species at chemical equilibrium. The numerical algorithm STEADYQL, which incorporates these principles, has been developed. This approach permits the calculation of sensitivity coefficients, that is, the partial derivative of the concentration of any species with respect to the value of any of the parameters that describe influx or efflux. The approach, which allows systematic and rapid computation of the speciation and sensitivity of any soil-water system, is illustrated with a simple example. A formal mathematical description of the method is given in an appendix.
Phospholipases A2 and Inflammatory Responses in the Central Nervous System

Phospholipases A2 (PLA2s) belong to a superfamily of enzymes responsible for hydrolyzing the sn-2 fatty acids of membrane phospholipids. These enzymes are known to play multiple roles for maintenance of membrane phospholipid homeostasis and for production of a variety of lipid mediators. Over 20 different types of PLA2s are present in the mammalian cells, and in snake and bee venom. Despite their common function in hydrolyzing fatty acids of phospholipids, they are diversely encoded by a number of genes and express proteins that are regulated by different mechanisms. Recent studies have focused on the group IV calcium-dependent cytosolic cPLA2, the group VI calcium-independent iPLA2, and the group II small molecule secretory sPLA2. In the central nervous system (CNS), these PLA2s are distributed among neurons and glial cells. Although the physiological role of these PLA2s in regulating neural cell function has not yet been clearly elucidated, there is increasing evidence for their involvement in receptor signaling and transcriptional pathways that link oxidative events to inflammatory responses that underline many neurodegenerative diseases. Recent studies also reveal an important role of cPLA2 in modulating neuronal excitatory functions, sPLA2 in the inflammatory responses, and iPLA2 with childhood neurologic disorders associated with brain iron accumulation. The goal for this review is to better understand the structure and function of these PLA2s and to highlight specific types of PLA2s and their cross-talk mechanisms in these inflammatory responses under physiological and pathological conditions in the CNS.
Potentiation of Disease-associated Cystic Fibrosis Transmembrane Conductance Regulator Mutants by Hydrolyzable ATP Analogs

The cystic fibrosis transmembrane conductance regulator (CFTR) is a chloride channel belonging to the ATP-binding cassette transporter superfamily. CFTR is gated by ATP binding and hydrolysis at its two nucleotide-binding domains (NBDs), which dimerize in the presence of ATP to form two ATP-binding pockets (ABP1 and ABP2). Mutations reducing the activity of CFTR result in the genetic disease cystic fibrosis. Two of the most common mutations causing a severe phenotype are G551D and ΔF508. Previously we found that the ATP analog N6-(2-phenylethyl)-ATP (P-ATP) potentiates the activity of G551D by ∼7-fold. Here we show that 2′-deoxy-ATP (dATP), but not 3′-deoxy-ATP, increases the activity of G551D-CFTR by ∼8-fold. We custom synthesized N6-(2-phenylethyl)-2′-deoxy-ATP (P-dATP), an analog combining the chemical modifications in dATP and P-ATP. This new analog enhances G551D current by 36.2 ± 5.4-fold suggesting an independent but energetically additive action of these two different chemical modifications. We show that P-dATP binds to ABP1 to potentiate the activity of G551D, and mutations in both sides of ABP1 (W401G and S1347G) decrease its potentiation effect, suggesting that the action of P-dATP takes place at the interface of both NBDs. Interestingly, P-dATP completely rectified the gating abnormality of ΔF508-CFTR by increasing its activity by 19.5 ± 3.8-fold through binding to both ABPs. This result highlights the severity of the gating defect associated with ΔF508, the most prevalent disease-associated mutation. The new analog P-dATP can be not only an invaluable tool to study CFTR gating, but it can also serve as a proof-of-principle that, by combining elements that potentiate the channel activity independently, the increase in chloride transport necessary to reach a therapeutic target is attainable.
Heats of binding protons to globular proteins.

The heats of binding of protons ΔHb to three globular proteins, lysozyme, chymotrysinogen A, and oxidized cytochrome c, from pH 11-2 or lower at 25°C were determined by flow microcalorimetry. In addition, the acid–base titrations of chymotrypsinogen A and oxidized cytochrome c were investigated under conditions similar to those used in the calorimetric experiments. The results of the calorimetric experiments and the acid–base titrations for lysozyme and chymotrypsinogen A in the neutral and alkaline pH regions are in accord with the Linderstrom-Lang model with a pH-independent electrostatic factor. However, in order to interpret the results on oxidized cytochrome c in the same pH region, it is necessary to assume the protonation of two unidentified groups; one of these groups, with ΔHb = −18 kcal/mol and pKa = 9.4 was detected in previous work [Watt, G. D. & Sturtevant, J. M. (1969) Biochemistry8, 4567]. The normal heats of protonation for carboxyl, ϵ-amino, phenolic, α-amino, and imidazole groups on globular proteins as deduced from the study are 0, −10.5, −6.3, −10.0, and −6.3 kcal/mol, respectively. ΔHb of chymotrypsinogen A between pH 4.5 and 1.3 is +30 kcal/mol. This value, which is undoubtedly too large to be accounted for by the protonation of normal carboxyl groups, leads to the conclusion that this protein undergoes a pH-induced conformational change in this pH region. The same idea can be applied to explain the abnormal ΔHb observed for oxidized cytochrome c in the alkaline pH region.
Integration of Three-Dimensional Scar Maps for Ventricular Tachycardia Ablation With Positron Emission Tomography-Computed Tomography

Objectives This study sought to assess the feasibility of deriving 3-dimensional (3D) scar maps from positron emission tomography (PET)/computed tomography (CT) hybrid imaging and to integrate those into clinical mapping systems to assist in ventricular tachycardia (VT) ablations. Background Ablation strategies for nonidiopathic VT are increasingly based on the anatomic information of the scar and its border zone. However, the current “gold standard” of voltage mapping is limited by its inability to accurately describe a complex 3D scar morphology, its imperfect spatial resolution, and prolonged procedure times. Methods Fourteen patients underwent PET/CT multimodality imaging before the VT ablation. We used PET/CT-derived scar maps to characterize myocardial scar using a 17-segment analysis and surface reconstruction. In 10 patients, reconstructed 3D metabolic scar maps were integrated into a clinical mapping system and compared with high-resolution voltage maps. Results A good correlation was found between the voltage maps and PET/CT-derived scar maps (r = 0.89; r Conclusions We found that PET/CT fusion imaging is able to accurately assess left ventricular scar and its border zone. The integration of a 3D scar map into a clinical mapping system is feasible and may allow supplementary scar characterization that is not available from voltage maps. This technique could significantly facilitate substrate-based VT ablations.
Cortisol regulation in posttraumatic stress disorder and major depression: a chronobiological analysis.

The aim of the present study was to evaluate the pattern of basal cortisol release in PTSD and major depression using a chronobiological analysis. Plasma for cortisol determination was obtained from 15 combat veterans with PTSD, 14 subjects with major depression, and 15 normal men every 30 min during a 24-hour period of bed rest. Raw cortisol data were modeled using standard and multioscillator cosinor models to determine the best fitting functions for circadian, hemicircadian, and ultradian components of cortisol release. PTSD subjects had substantially lower cortisol levels, and displayed a pattern of cortisol release that was better modeled by circadian rhythm. PTSD subjects also showed a greater circadian signal-to-noise ratio than the other groups. In contrast, depressed patients displayed a less rhythmic, more chaotic pattern of cortisol release. The pattern of cortisol secretion and regulation observed in the PTSD group under baseline conditions may reflect an exaggerated sensitization, whereas the chronobiological alterations in depression may reflect dysregulation, of the hypothalamic-pituitary-adrenal (HPA) axis.
The extracytoplasmic linker peptide of the sensor protein SaeS tunes the kinase activity required for staphylococcal virulence in response to host signals.

Bacterial pathogens often employ two-component systems (TCSs), typically consisting of a sensor kinase and a response regulator, to control expression of a set of virulence genes in response to changing host environments. In Staphylococcus aureus, the SaeRS TCS is essential for in vivo survival of the bacterium. The intramembrane-sensing histidine kinase SaeS contains, along with a C-terminal kinase domain, a simple N-terminal domain composed of two transmembrane helices and a nine amino acid-long extracytoplasmic linker peptide. As a molecular switch, SaeS maintains low but significant basal kinase activity and increases its kinase activity in response to inducing signals such as human neutrophil peptide 1 (HNP1). Here we show that the linker peptide of SaeS controls SaeS’s basal kinase activity and that the amino acid sequence of the linker peptide is highly optimized for its function. Without the linker peptide, SaeS displays aberrantly elevated kinase activity even in the absence of the inducing signal, and does not respond to HNP1. Moreover, SaeS variants with alanine substitution of the linker peptide amino acids exhibit altered basal kinase activity and/or irresponsiveness to HNP1. Biochemical assays reveal that those SaeS variants have altered autokinase and phosphotransferase activities. Finally, animal experiments demonstrate that the linker peptide-mediated fine tuning of SaeS kinase activity is critical for survival of the pathogen. Our results indicate that the function of the linker peptide in SaeS is a highly evolved feature with very optimized amino acid sequences, and we propose that, in other SaeS-like intramembrane sensing histidine kinases, the extracytoplasmic linker peptides actively fine-control their kinases.
The dialyzable free organic constituents of squid blood; a comparison with nerve axoplasm.

Abstract The dialyzate of the blood of the squid Loligo pealii was analyzed quantitatively for its free organic constituents for comparison with the composition of the axoplasm of Loligo nerves previously determined. Somewhat unexpectedly all substances found in axoplasm, with the exception of the group of peptides, were found also in blood. However, the concentrations of organic anions, taurine, and betaine in axoplasm were fifty to a hundred times as high as in blood. The ratios of concentrations in axoplasm and blood showed no constancy or pattern presently interpretable in terms of function or structure.
Quadratic divergence of geodesics in CAT(0) spaces

A finite CAT(0) 2-complexX is produced whose universal cover possesses two geodesic rays which diverge quadratically and such that no pair of rays diverges faster than quadratically. This example shows that an aphorism in Riemannian geometry, that predicts that in nonpositive curvature nonasymptotic geodesic rays either diverge exponentially or diverge linearly, does not hold in the setting of CAT(0) complexes. The fundamental group ofX is that of a compact Riemannian manifold with totally geodesic boundary and nonpositive sectional curvature.
Quadropolar interactions and the magnetic states of HoSb

Abstract The magnetic phase diagrams of a HoSb crystal, for fields along various axes, are found to contain antiferromagnetic and ferrimagnetic regimes similar to those of DySb and thus offer analogous evidence for strong quadrupolar interactions. Such interactions are also revealed by analysis of magnetization-field isotherms above the Neel point.