cssi/SciSciGPT-SciSciNet huggingface dataset:
New means, new measures: assessing prescription drug-seeking indicators over 10 years of the opioid epidemic.

BACKGROUND AND AIMS Prescription drug-seeking (PDS) from multiple prescribers is a primary means of obtaining prescription opioids; however, PDS behavior has probably evolved in response to policy shifts, and there is little agreement about how to operationalize it. We systematically compared the performance of traditional and novel PDS indicators. DESIGN Longitudinal study using a de-identified commercial claims database. SETTING United States, 2009-18. PARTICIPANTS A total of 318 million provider visits from 21.5 million opioid-prescribed patients. MEASUREMENTS We applied binary classification and generalized linear models to compare predictive accuracy and average marginal effect size predicting future opioid use disorder (OUD), overdose and high morphine milligram equivalents (MME). We compared traditional indicators of PDS to a network centrality measure, PageRank, that reflects the prominence of patients in a co-prescribing network. Analyses used the same data and adjusted for patient demographics, region, SES, diagnoses and health services. FINDINGS The predictive accuracy of a widely used traditional measure (N + unique doctors and N + unique pharmacies in 90 days) on OUD, overdose and MME decreased between 2009 and 2018, and performed no better than chance (50% accuracy) after 2015. Binarized PageRank measures however exhibited higher predictive accuracy than the traditional binary measures throughout 2009-2018. Continuous indicators of PDS performed better than binary thresholds, with days of Rx performing best overall with 77-93% predictive accuracy. For example, days of Rx had the highest average marginal effects on overdose and OUD: a 1 standard deviation increase in days of Rx was associated with a 6-8% [confidence intervals (CIs) = 0.058-0.061 and 0.078-0.082] increase in the probability of overdose and a 4-5% (CIs = 0.038-0.043 and 0.047-0.053) increase in the probability of OUD. PageRank performed nearly as well or better than traditional indicators of PDS, with predictive performance increasing after 2016. CONCLUSIONS In the United States, network-based measures appear to have increasing promise for identifying prescription opioid drug-seeking behavior, while indicators based on quantity of providers or pharmacies appear to have decreasing utility.
Deductive Parsing: The Use of Knowledge of Language

Current linguistic theory distinguishes a competent speaker’s knowledge of a language from the way in which that knowledge is used. This chapter describes a framework for modeling the relationship between knowledge of language and its use. The ‘Parsing as Deduction’ framework1 models knowledge of a language as an axiom system, and knowledge about the utterances of that language as logical consequences of these axioms. The use of knowledge of a language to generate knowledge about some particular utterance can then be regarded as the deduction of the relevant consequences in the theory defined by the axioms.
Titanium wear debris in failed cemented total hip arthroplasty. An analysis of 71 cases.

Abstract Seventy-one cemented total hip arthroplasties (THAs) were reviewed following removal of the all-titanium alloy femoral stem. Fifty-one hips were primary arthroplasties that failed due to aseptic loosening, 8 were previous revisions with aseptic loosening, and 12 were removed for infection. The average duration of service for the three groups was 4.5 years, 5.0 years, and 3.7 years, respectively. Femoral bone loss in aseptically loose, primary THA was graded as severe in 51%, moderate in 24%, and mild in 20%. Femoral endosteolysis was present in 94%, while acetabular osteolysis was seen in 6%. Histological evaluation of tissues from failed primary arthroplasties revealed polymethyl methacrylate debris in 75% of cases, polyethylene debris in 80%, metal debris in 75%, and chronic inflammatory cells in all cases. Metallic debris was not seen in the failed revision cases and in only 17% of the infected cases. Examination of retrieved femoral components revealed burnishing of the head in all cases, while 71% of stems with aseptic loosening were abraded from the cement. Metal levels from 12 cases averaged 2,111 mg/g of dry tissue (range, 60–11,823); synovial fluid levels from 8 other cases averaged 106 mg/l (range, 22–340). While it is not certain whether metallic particles are a primary cause of loosening or are generated secondarily, their presence seems to accelerate bone loss and loosening.
Thermodynamics of Protein‐Ligand Interactions

Originally published in: Protein-Ligand Interactions.Edited by Hans-Joachim Bohm, Gisbert Schneider. Copyright © 2003 Wiley-VCH Verlag GmbH & Co. KGaA Weinheim. Print ISBN: 3-527-30521-6 The sections in this article are Introduction Basic Thermodynamics of Protein-Ligand Interactions Measurement of Thermodynamic Parameters Calorimetric Determination of Thermodynamic Parameters van't Hoff Determination of Thermodynamic Parameters Relationship to Equilibrium Constant Obtaining the Equilibrium Constant Applications Calorimetric Determination of Thermodynamic Parameters van't Hoff Determination of Thermodynamic Parameters Caveats Summary Keywords: drug design; experimental approaches; thermodynamics; parameters; protein-ligand interactions; calorimetric determination; van't Hoff determination; equilibrium constant; caveats
Native American Free Passage Rights Under the 1794 Jay Treaty: Survival Under United States Statutory Law and Canadian Common Law

Since 1794, Native American groups in both the United States (U.S.) and Canada have enjoyed the right of "free passage" across the U.S.-Canadian border per the provisions of the Jay Treaty. However, development and recognition of this right have taken decidedly different courses: while the U.S. has treated the right very liberally under statutory codification, the Canadian government has opted to develop, and restrict, the right under their courts' common law. This Note discusses the origin and development of the "free passage" right under the Jay Treaty, and encourages both the continued recognition of the right, as well as a stronger Canadian common law effort to harmonize treatment of the right with U.S. jurisprudence.
Silene stereochemistry. IV: The configurational stability of 1-phenyl-1-methyl-2-neopentylsilene under flash vacuum thermolysis conditions

Abstract When E - or Z -1-phenyl-1-methyl-2-neopentylsilene is generated by retro Diels-Alder flash vacuum thermolysis of their corresponding cyclopentadiene or anthracene adducts at temperatures between 400 and 650°C and trapped with 2,3-dimethyl-1,3-butadiene, the stereochemical distribution of the products is independent of the stereochemistry of the silene precursor indicating that the silene is not configurationally stable towards cis-trans isomerization at these temperatures. Evidence that intermolecular “ene” reaction and the [4 + 2] cycloaddition which occur between silenes and the diene are both concerted reactions is presented.
Transgender Identity and Suicidality in a Nonclinical Sample

Abstract This study examined the relation between sexual orientation and suicidality among 73 transgender respondents, who were compared to heterosexual females (n = 1,083) and males (n = 1,077), psychosocially matched females (n = 73) and males (n = 73), and homosexual females (n = 256) and males (n = 356). Significantly more (p < .05)transgender respondents reported suicide ideation and attempts than any group except homosexual females. Sexual orientation did not differentiate transgender ideators or attempters from non-ideators or non-attempters. Attempters were more likely than non-attempters to report psychotherapy and psychiatric medications currently and previously as well as difficulties with both alcohol and drugs (attempters and ideators) or alcohol only (attempters). Implications for gender studies as well as research regarding suicide and sexual orientation are discussed.
Heterogeneity in intratumor distribution of p53 mutations in human prostate cancer.

Abstract Prostatic carcinoma from 65 patients have been examined for the occurrence of point mutations in the p53 tumor suppressor gene locus within the region of exons 5 to 8. Overall, only a small fraction of tumors (12.3%) was found to contain p53 mutations. No significant correlation was detected between the presence of the mutant gene and either tumor volume or histopathological grade. However, metastatic prostatic tumors are found to display a higher percentage (21.4%) of p53 mutations compared with primary adenocarcinomas (9.8%). Analysis of the topographical distribution of the p53 mutant genotype revealed two remarkable findings. First, multifocal tumors within a prostate appear to differ in harboring the mutant gene, and second, evidence is obtained for intratumor heterogeneity in the distribution of the mutant p53 allele. Together these findings appear to explain, at least in part, why there has been a wide discrepancy in the reported detection frequency of p53 mutations in prostate cancer specimens. It appears that the outcome of mutation analysis would depend not only on which tumors but also which regions of the tumors are included in the study. Furthermore, the observed heterogeneous topographical distribution of the mutation, if confirmed to be unique to prostate cancer, may have important implications in the understanding of the biology of prostate carcinogenesis.
Kinematics of the Galactic globular cluster system

Constraints on cluster kinematics proper motions, radial velocities and tidal radii are reviewed. Analysis of the cluster radial velocity distribution suggests a rotation law for the system in which the specific angular momentum is nearby independent of galactocentric distance, and the residual velocity dispersion is isotropic. However, the absence of severely tidally truncated clusters indicates that nearly radial orbits are absent from this distribution. The kinematic properties of the remote halo clusters remain largely indeterminate. Absolute proper motions measured directly with respect to background galaxies and quasars are needed to determine the kinematics of these objects, and also to elucidate the process of tidal stripping.
A Cure Worse than the Disease

The pending challenge to section 5 of the Voting Rights Act insists the statute is no longer necessary. Should the Supreme Court agree, its ruling is likely to reflect the belief that section 5 is not only obsolete but that its requirements do more harm today than the condition it was crafted to address. This short essay examines why the Court might liken section 5 to a destructive treatment and why reliance on that analogy in the pending case threatens to leave the underlying condition unaddressed and Congress without the power to address it.
Telework rationale and implementation for people with disabilities: considerations for employer policymaking.

Background Telework has been promoted as a viable workplace accommodation for people with disabilities since the 1990s, when information and communication technologies (ICT) had developed sufficiently to facilitate its widespread adoption. This initial research and accompanying policy recommendations were prescriptive in nature and frequently aimed at employers. Objective This article adds to existing policy models for facilitating successful telework outcomes for people with disabilities. Drawing upon two studies by the Rehabilitation Engineering Research Center on Workplace Accommodations, we expound on employee-side considerations in the implementation of telework. Methods Our policy model utilizes established typologies for policy evaluation to develop a process model that considers rationales and implementation factors for telework among people with physical disabilities. Results Telework may be used as an accommodation for disability, but employee rationales for telework are more complex, involving work-life balance, strategies for pain and fatigue not formally recognized as disability, and expediency in travel and transportation. Implementation of telework as a component of workplace operations is similarly multifaceted, involving non-technology accommodations to realize job restructuring left incomplete by telework. Conclusions Our model grounds new empirical research in this area. We also renew our call for additional research on effective telework practices for people with disabilities.
T118M PMP22 as a Modifier for Hereditary Neuropathy with Liability to Pressure Palsy (HNPP) (P2.063)

OBJECTIVE: To demonstrate T118M PMP22 as a modifier for Hereditary Neuropathy with Liability to Pressure Palsy (HNPP). BACKGROUND: HNPP is a common genetic neuropathy caused by the heterozygous deletion of PMP22 on chromosome 17. Patients have a typical phenotype with focal episodes of weakness and/or sensory loss and nerve conduction slowing at common compression sites. The T118M PMP22 mutation causes minimal deficits itself but has been reported to cause partial loss of PMP22 function. DESIGN/METHODS: A 6 year old girl with HNPP and the T118M PMP22 was evaluated by clinical and neurophysiological studies. RESULTS: The proband was the product of a 35 week twin delivery, stayed 2.5 weeks in the NICU for respiratory and feeding difficulties, but then had a benign neonatal course. She reached her milestones on time and walked at 13 months. At 3.5 years, she tripped climbing stairs and caught her toes on the ground while ambulating. At 4.5 years, her feet turned inwards and she developed foot pain and cramps. At age 6, she could walk only with braces. Examination revealed severe tibialis anterior atrophy, and weakness in the tibialis anterior and peroneus longus (1/5) bilaterally. She had tight Achilles tendons and couldn’t toe, heel, or tandem walk. Reflexes were reduced or absent. Cranial nerves, mentation, sensation and strength in her upper extremities were normal. The CMT pediatric score was 26, indicating moderate impairment. Nerve conduction studies were in the demyelinating range with an ulnar nerve conduction velocity at 35 m/s; there were compressive mononeuropathies of the bilateral median nerves at the wrist and ulnar nerves at the elbow. CONCLUSIONS: Her severe presentation of HNPP is the likely consequence of the T118M PMP22 mutation as all other genetic testing was normal. These results evidence that mutations like T118M PMP22 can influence disease severity even if they cause minimal impairment by themselves. Disclosure: Dr. Jerath has nothing to disclose. Dr. Grider has nothing to disclose. Dr. Swenson has nothing to disclose. Dr. Shy has nothing to disclose.
Joint MiRNA/mRNA expression profiling reveals changes consistent with development of dysfunctional corpus luteum after weight gain

Obese women exhibit decreased fertility, high miscarriage rates and dysfunctional corpus luteum (CL), but molecular mechanisms are poorly defined. We hypothesized that weight gain induces alterations in CL gene expression. RNA sequencing was used to identify changes in the CL transcriptome in the vervet monkey (Chlorocebus aethiops) during weight gain. 10 months of high-fat, high-fructose diet (HFHF) resulted in a 20% weight gain for HFHF animals vs. 2% for controls (p = 0.03) and a 66% increase in percent fat mass for HFHF group. Ovulation was confirmed at baseline and after intervention in all animals. CL were collected on luteal day 7–9 based on follicular phase estradiol peak. 432 mRNAs and 9 miRNAs were differentially expressed in response to HFHF diet. Specifically, miR-28, miR-26, and let-7b previously shown to inhibit sex steroid production in human granulosa cells, were up-regulated. Using integrated miRNA and gene expression analysis, we demonstrated changes in 52 coordinately regulated mRNA targets corresponding to opposite changes in miRNA. Specifically, 2 targets of miR-28 and 10 targets of miR-26 were down-regulated, including genes linked to follicular development, steroidogenesis, granulosa cell proliferation and survival. To the best of our knowledge, this is the first report of dietary-induced responses of the ovulating ovary to developing adiposity. The observed HFHF diet-induced changes were consistent with development of a dysfunctional CL and provide new mechanistic insights for decreased sex steroid production characteristic of obese women. MiRNAs may represent novel biomarkers of obesity-related subfertility and potential new avenues for therapeutic intervention.
Effects of renal denervation on the sodium excretory actions of leptin in hypertensive rats.

Effects of renal denervation on the sodium excretory actions of leptin in hypertensive rats. Background Previous studies from this laboratory have reported a marked attenuation of the renal responses to pharmacologic doses of synthetic murine leptin infused in the spontaneously hypertensive rat (SHR) model compared with normotensive Sprague-Dawley and lean Zucker rat models. Methods In the present study, the hemodynamic and renal excretory effects of an intravenous bolus administration of pharmacologic doses of synthetic murine leptin were examined in groups of anesthetized SHR with unilateral nephrectomy and renal denervation or sham-denervation of the remaining kidney. Results In the SHR with acute renal denervation ( N = 8), an intravenous bolus of 1600 μg/kg of leptin produced a significant twofold to fourfold elevation in sodium excretion but did not increase natriuresis in the sham-denervated group ( N = 6). Chronic renal denervation of one-week duration ( N = 8) was associated with qualitatively and quantitatively similar increases of sodium excretion in response to leptin administration. Mean arterial pressure remained unchanged in all groups after the administration of leptin. Conclusions Collectively, these results are interpreted to suggest that the blunted natriuretic and diuretic responses to leptin observed in the SHR with intact renal nerves may be partially explained by the antinatriuretic effect of an enhanced baseline efferent renal sympathetic activity and/or leptin's stimulation of the sympathetic nervous system.
The insertion of 3-buten-1-OL into metal—alkyl bonds utilizing typical titanium—aluminum ziegler—natta catalysts

Abstract The alkylation of 3-buten-1-ol with organoaluminum reagents promoted by titanium compounds was studied. With ethylaluminum compounds 3- buten-1-ol was alkylated in the presence of TICl4, Cp2TiCl2, and Ti(acac)2Cl2 to give varying mixtures of 1-hexanol, 3-methyl-1-pentanol, and trans-3- hexen-1-ol.
The GIS Forma Urbis Romae Project: Creating a Layered History of Rome

Using advanced GIS technology and accepted scholarly methods, this multi-disciplinary project intends to create a layered history of Rome by updating Forma Urbis Romae, the cartographic masterpiece of ancient Roman topography published in 1901 by archeologist Rodolfo Lanciani. This extremely accurate map measures 25 by 17 ft and uses an innovative graphic system that represents Rome’s historic urban fabric as a series of transparent layers from ancient to modern. The map remains the standard archeological reference for Rome even though it does not incorporate archeological discoveries uncovered since its original publication 100 years ago. We plan to critically examine, update and eventually republish the map as an interactive website that will also serve as a dynamic geo-database for scholars and others. Our project team will bring its considerable experience in web-based design in the study of the humanities to ensure a highly intuitive product that is accessible, interactive and expandable.
Creating a Culture of Data Use for Continuous Improvement: A Case Study of an Edison Project School

Abstract In this article, I outline how, with the appropriate mix of external requirements and internal motivation, structure and capacity, a school can promote and maintain a culture of evaluative practices, specifically data use, for continuous improvement. I draw upon qualitative data conducted in a study of an Edison Project school. The findings from this paper are the result of a larger 4-year study examining Comprehensive School Reform in 12 Title 1 schools in three states. Interviews were conducted with principals, teachers, other staff, parents and students, as well as with state officials, the superintendent, assistant superintendent and other high level administrators in the district. Observations were undertaken at the classroom level. Key findings include the importance of obtaining a multidimensional view of educational change. That is, we need to obtain a picture of the school reform environment (i.e., interconnections between the state, district, and school levels), and simultaneously investigate the interplay among critical school levers that are required to promote and maintain a culture of data use for school improvement. From this multidimensional view, we are better positioned to investigate and evaluate school change efforts.
Mechanical characterization of soft viscoelastic gels via indentation and optimization-based inverse finite element analysis.

Abstract Polymer gels are widely accepted as candidate materials for tissue engineering, drug delivery, and orthopedic load-bearing applications. In addition, their mechanical and physical properties can be tailored to meet a wide range of design requirements. For soft gels whose elastic modulus is in the kPa range, mechanical characterization by bulk mechanical testing methods presents challenges, for example, in sample preparation, fixture design, gripping, and/or load measurement accuracy. Nanoindentation, however, has advantages when characterizing the mechanical properties of soft materials. This study was aimed at investigating the application of an inverse finite element analysis technique to identify material parameters of polymer gels via nanoindentation creep testing, optimization, and finite element simulation. Nanoindentation experiments were conducted using a rigid circular flat punch, and then simulated using the commercial software ABAQUS™. The optimization (error minimization) procedure was integrated in the parameter determination process using a Matlab™ shell program, which makes this approach readily adaptable to other test geometries and material models. The finite element results compare well with a derived analytical viscoelastic solution for a rigid circular flat punch on a Kelvin–Voigt half-space.
On the Joint Effect of Baroclinicity and Topography

Abstract A simple two-layer model is constructed to illustrate the combined effect of baroclinicity and topography over an idealized continental slope region. It is shown that an assumed thermohaline circulation leads to topographic vorticity contributions in the southward flowing deep current with the concomitant enhancement of the western boundary transport computed by Holland (1973).
Understanding protein structure-function relationships in Family 47 α-1,2-mannosidases through computational docking of ligands

Family 47 alpha-1,2-mannosidases are crucial enzymes involved in N-glycan maturation in the endoplasmic reticula and Golgi apparati of eukaryotic cells. High-resolution crystal structures of the human and yeast endoplasmic reticulum alpha-1,2-mannosidases have been recently determined, the former complexed with the inhibitors 1-deoxymannojirimycin and kifunensine, both of which bind in its active site in the unusual 1C4 conformation. However, unambiguous identification of the catalytic proton donor and nucleophile involved in glycoside bond hydrolysis was not possible from this structural information. In this work, alpha-D-galactose, alpha-D-glucose, and alpha-D-mannose were computationally docked in the active site in the energetically stable 4C1 conformation as well as in the 1C4 conformation to compare their interaction energetics. From these docked structures, a model for substrate and conformer selectivity based on the dimensions of the active site was proposed. Alpha-D-galactopyranosyl-(1-->2)-alpha-D-mannopyranose, alpha-D-glucopyranosyl-(1-->2)-alpha-D-mannopyranose, and alpha-D-mannopyranosyl-(1-->2)-alpha-D-mannopyranose were also docked into the active site with their nonreducing-end residues in the 1C4 and E4 (representing the transition state) conformations. Based on the docked structure of alpha-D-mannopyranosyl-E4-(1-->2)-alpha-D-mannopyranose, the catalytic acid and base are Glu132 and Glu435, respectively.
Prospective comparison of Congo red and sham feeding testing to determine vagal innervation of the stomach

Abstract The purpose of this study was to validate Congo red (CR) testing as a means of determining the status of vagal innervation of the stomach after gastric surgery by comparing it with the sham feeding test (SF). Twenty-six patients with previous gastric operations were studied prospectively. The operations were vagotomy/antrectomy (n = 14), vagotomy/ antrectomy/Roux-en-Y anastomosis (n = 4), proximal gastric vagotomy (n = 3), vagotomy/pyloroplasty (n = 2), and antireflux (n = 3). In each case, the CR test was performed prior to the SF test so that the endoscopist was unbiased. The CR test solution was sprayed on the gastric mucosa through a wash catheter and immediately aspirated. A two-dimensional map of the endoscopist's conception of the red and black mucosa was drawn, and areas were calculated using a computerized scanner. The SF test was performed as described previously, with sham/peak ratios (sham feeding stimulated acid output [SAO]/peak acid output [PAO]) greater than 0.1 indicating a positive test, or incomplete vagotomy. The CR test was negative in 11 patients and positive in 15 patients. SF was negative in 16 patients (SAO/PAO of less than 0.1) and positive in 10 patients. The results correlated in 18 of 26 (69%) patients (p = not significant). Positive sham feeding tests and negative Congo red tests were more reliable, whereas negative sham feeding tests and positive Congo red tests were less reliable. Except patients with Roux-en-Y anastomosis, patients with negative or weakly positive CR tests did not have recurrent ulcers or other symptoms attributable to acid hypersecretion. The CR test was easier to perform and preferred by the patients. We conclude that both tests provide valuable clinical information and that both tests should be available in the evaluation of postgastrectomy patients.
PHARMACOKINETICS OF HYDROCORTISONE (HC) IN EXTREMELY LOW BIRTHWEIGHT (ELBW) INFANTS IN THE FIRST WEEK OF LIFE. † 1493

PHARMACOKINETICS OF HYDROCORTISONE (HC) IN EXTREMELY LOW BIRTHWEIGHT (ELBW) INFANTS IN THE FIRST WEEK OF LIFE. † 1493
Strategic implementation: Five approaches to an elusive phenomenon

The traditional textbook approach to strategy implementation was to treat ‘implementation’ as an activity following ‘formulation’. Usually, the topic was treated as a question of organization design, where systems and structures were manipulated in concert with strategic goals. More recent views treat implementation either as an issue of gaining prior group commitment through coalitional decision-making, or as a question of total organizational involvement through a strong corporate culture. This paper reviews the evolution of these approaches, developing four models to characterize them, and suggests a fifth one, with strategy emerging in an almost-implemented form from within the firm.
SU‐FF‐I‐70: Asymmetric Spin Echo in FMRI at 3T: A Quantitative Evaluation of BOLD Response and Signal Drop Off

Purpose: To quantitatively evaluate the fMRI BOLD response of the asymmetric spin echo(ASE) EPI acqusition and signal drop offs at 3T. Applications in the frontal cortical and orbital frontal cortical (OFC) areas from finger tapping and olfactory stimulation were investigated. Method and Materials:ASE EPI was developed and tested on a 3.0T scanner. Phantom was used for quantitative distortion measurement by the GRE‐, SE‐, and ASE‐EPI sequences. For olfactory testing, subjects were presented with 12s of olfactory stimuli interspersed by 28s of air with a total scan time of 7 minutes. Subjects were trained to inhale and exhale following a prompts on the screen. Eight subjects were studied for finger tapping and six subjects for olfactory. The BOLD intensity and correlation were measured in the frontal cortical area for finger tapping, and in the orbital frontal area for olfactory stimulation studies. Results: The signal drop off is relatively small when the echo shift is 5 msec and 10 msec compare to SE‐EPI, but is significantly better compared to GRE‐EPI. The optimal BOLD response from olfactory test was detected by ASE with 35 msec TE, and 10 msec echo shift. Almost no BOLD effect detected from SE at TE of 35 ms and with ASE at TE of 35 ms and 5 ms echo shift. Echo shift of 15 msec had strong artifacts. GRE‐EPI was not useable for the olfactory study because almost all the signal dropped off in the OFC area. Conclusions: ASE‐EPI offers reasonable BOLD response without significant reduction in the slice coverage like SE‐EPI. It can detect BOLD response where the signal is small and susceptibility is strong. GRE‐EPI is preferred when the BOLD response is located in the less susceptible areas. ASE‐EPI with 10 msec echo shift appears to be optimal for olfactory study at 3T.
Quantification of absolute myocardial perfusion at rest and during exercise with positron emission tomography after human cardiac transplantation.

Abstract The maximal exercise capacity of cardiac transplant recipients is reduced compared with that of normal subjects. To determine if this reduced exercise capacity is related to inadequate myocardial perfusion during exercise, myocardial perfusion was measured noninvasively with use of positron emission tomography and nitrogen (N)-13 ammonia. Twelve transplant recipients with no angiographic evidence of accelerated coronary atherosclerosis were studied. Serial N-13 ammonia imaging was performed at rest and during supine bicycle exercise. The results were compared with those from 10 normal volunteers with a low probability of having cardiac disease. A two-compartment kinetic model for estimating myocardial perfusion was applied to the data. Transplant recipients achieved a significantly lower exercise work load than did the volunteers (42 ± 16 vs. 128 ± 22 W), but a higher venous lactate concentration (31.3 ± 14.9 vs. 13.7 ±4.1 mg/100 ml). Despite the difference in exercise work load, there was no significant difference in the cardiac work achieved by transplant recipients and normal subjects as evidenced by similar rate-pressure products of 24,000 ± 3,400 versus 21,300 ±2,800 beats/min per mm Hg, respectively. In addition, myocardial blood flow during exercise was not significantly different between the two groups (1.70 ± 0.60 vs. 1.56 ± 0.71 ml/min per g, respectively). This study demonstrates that the myocardial flow response to the physiologic stress of exercise is appropriate in transplant recipients and does not appear to explain the decreased exercise capacity in these patients.
Mechanisms of31P relaxation in phosphorus metabolites

Measurements have been made of the longitudinal relaxation timeT1 of31P for the individual resonances of the metabolites AMP, ADP, ATP, Pir and PCr (phosphocreatine) in H2O and D2O solutions from 5 to 60°C at various concentrations and at frequencies of 40 MHz (2.3 T) and 120 MHz (7 T). The contributions of dipolar, chemical shift anisotropy, and spin-rotation mechanisms have been separated, and activation parameters of the underlying molecular reorientations have been determined.
Farmland preservation and sustainable agriculture: grassroots and policy connections.

Over the long run, a sustainable food production system requires both a sufficient base of agricultural land and agricultural practices that do not degrade the land. However, current policies and programs for protecting agricultural land are not systematically integrated with those promoting sustainable agriculture. There are various ways that policymakers, agricultural support organizations, and researchers could better integrate farmland preservation and sustainable agriculture efforts. This paper suggests several approaches for developing such connections including: coordinating local, state, and federal policies, conducting related research, and developing integrated outreach and education programs.
Impact of matching networks on direction finding performance utilizing two closely spaced electrically small antennas

Direction of arrival (DOA) of a microwave signal is important for many commercial and military applications. Accurate DOA estimation technique with small system size is highly desirable. Electrically small antenna array with small spacing between any two adjacent antennas is attractive because of the compact size of the whole system. The challenge is how to achieve high accuracy of DOA estimation under this circumstance.
Cowardice and paralysis: A brief glance at some of Arthur Schnitzler's male characters

A significant number of Schnitzler’s male characters, from the early Anatol to the late Falkenir (Komodie der Verfuhrung), behave in a way that can readily be termed as cowardly. This behavior involves both literal fleeing and a simple avoidance of what a character may deem to be an unpleasant or deleterious situation. Another aspect of this behavior demonstrated by a number of characters, particularly by Dr. Grasler (Doktor Grasler, Badearzt), suffer from the sort of paralysis – the inability to act in one’s own or another person’s best interest – that seems to inform much of twentieth century literature. Regardless of the form their cowardice takes, the characters end up alone, unable to connect to another human being.
The effect of D-cycloserine on subliminal cue exposure in spider fearful individuals.

Research on d-cycloserine (DCS) has demonstrated a significant effect on symptom reduction in human studies that utilized conventional exposure-based approaches. Recent studies have offered promising results for targeting fears through subliminal paradigms. In this double-blind, randomized placebo-controlled study, 45 spider fearful individuals received DCS or placebo pills prior to completing a subliminal cue exposure task to images of spiders. Participants completed self-report questionnaires and a behavioral approach task to a live caged tarantula. After repeated exposure to subliminal spider cues, participants in the DCS group reported a greater reduction in disgust than individuals in the placebo group. No difference was observed in fear ratings. These findings suggest that DCS augments the reduction in disgust in spider fearful subjects after subliminal exposure to spider cues.
TGF-β1 reduces the heterogeneity of astrocytic cyclooxygenase-2 and nitric oxide synthase-2 gene expression in a stimulus-independent manner

Transforming growth factor-β1 (TGF-β1) is upregulated by inflammatory mediators in several neurological diseases/disorders where it either participates in the pathology or provides protection. Often, the biological outcome of TGF-β1 is dependent upon changes in gene expression. Recently, we demonstrated that TGF-β1 enhances astrocytic nitric oxide production induced by lipopolysaccharide (LPS) plus interferon-γ (IFNγ) by increasing the number of astrocytes in a population that express NOS-2. The purpose of this study was two-fold: 1) to determine whether this effect occurs more generally by assessing the effect of TGF-β1 on another pro-inflammatory gene, cyclooxygenase-2 (COX-2); and 2) to assess stimulus specificity. We found that TGF-β1 augmented LPS plus IFNγ-induced COX-2 mRNA and protein expression, by nearly tripling the number of astrocytes that express COX-2. The effect was not stimulus-specific as TGF-β1 enhanced the number of astrocytes that expressed both COX-2 and NOS-2 protein when either IL-1β or TNFα was used in lieu of LPS. Collectively, these results suggest that TGF-β1 augments overall protein expression levels of select pro-inflammatory genes in astrocytes in a promiscuous manner by reducing the magnitude of noise in the cellular population.
Self-Calibrating Priors Do Not Exist

Abstract It is shown that self-calibrating priors in the sense of Dawid (1982a) do not exist.
On-line separation and identification of inorganic and organic arsenic species in ethanolic kelp and bladderwrack extracts through liquid chromatography/particle beam-electron ionization mass spectrometry (LC/PB-EIMS)

Ion-pair, reversed-phase high-performance liquid chromatography (IP-RP-HPLC) and ion exchange chromatography (IEC), coupled to particle beam-electron ionization mass spectrometry (PB-EIMS), are employed for the separation and identification of inorganic and organic arsenic compounds (As (III) chloride, arsenobetaine (AB), dimethylarsinic acid (DMA) and an arsenosugar (oxo-arsenosugar-glycerol, As 328) in commercial ethanolic kelp and bladderwrack extracts. The reversed-phase separation was performed on a C18 column using an isocratic mobile phase composition of water:methanol (96:4) containing 0.1% of trifluoroacetic acid (TFA) as an ion-pairing agent. The flow rate was optimized at 0.7 mL min−1 and the separation accomplished in less than 8 minutes. Baseline resolution was achieved in an elution window of about 4 minutes. The ion-exchange separation was performed on an anion-exchange column using a gradient mobile phase composition of 0.5 mM nitric acid containing 2% methanol and 50 mM nitric acid. The separation was accomplished in less than 8 minutes at a flow rate of 0.9 mL min−1. The eluted species were detected and identified using a PB-EIMS system providing species-specific information. The influence of various instrument parameters was evaluated to achieve optimal mass spectrometric response for the test compounds. The absolute detection limits of arsenic species with HPLC/PB-EIMS were 0.03, 0.05, 0.008 ng and 0.005 (5 µL injection) in the SIM mode and 0.1, 0.14, 0.04 and 0.01 ng in the TIC mode for As (III), DMA, AB and As 328 respectively. These investigations revealed that the majority (90–95%) of the arsenic present in the ethanolic extract samples is in the form of inorganic arsenic, with minor amounts of As (5–10% of the total As) present in the form of DMA. There were no detectable levels of AB and arsenosugars. The total arsenic content in the ethanolic extracts was verified by ICP-OES and validated by analyzing NIST SRM 3241 Ephedra sinica Stapf Native Extract and SRM 3243 Ephedra-Containing Solid Oral Dosage Form. These investigations indicate that PB-EIMS is a viable approach for comprehensive speciation of various botanical extracts.
Control-Theoretic Methods for Cyberphysical Security: Geometric Principles for Optimal Cross-Layer Resilient Control Systems

Cyberphysical systems integrate physical processes, computational resources, and communication capabilities. Cyberphysical systems have permeated modern society, becoming prevalent in many domains, including energy production, health care, and telecommunications. Examples of cyberphysical systems include sensor networks, industrial automation systems, and critical infrastructures such as transportation networks, power generation and distribution networks, water and gas distribution networks, and advanced manufacturing systems. The integration of cybertechnologies with physical processes increases system efficiencies and, at the same time, introduces vulnerabilities that undermine the reliability of critical infrastructures. As recently highlighted by the Maroochy water breach in March 2000 [1], multiple recent power blackouts in Brazil [2], the SQL Slammer worm attack on the Davis-Besse nuclear plant in January 2003 [3], the StuxNet computer worm in June 2010 [4], and various industrial security incidents [5], cyberphysical systems are prone to failures and attacks on their physical infrastructure and cyberattacks on their data management and communication layer [6], [7].
Neuronal control of post‐coital pheromone production in the moth Heliothis virescens

The mechanism involved in bringing about post-coital suppression of pheromone production, pheromonostasis, was studied in the noctuid moth Heliothis virescens. Mating results in a transient suppression in pheromone production, the signal for which appears to originate in the testes and other components of the male's reproductive system. The mating-induced pheromonostasis is due to an ascending signal via the central nervous system that appears to inhibit the release of the pheromonotropin, pheromone biosynthesis activating neuropeptide (PBAN), or other potential pheromonotropic substances, and is not due to a refractoriness in response of the sex pheromone glands to PBAN in the female. A similar mechanism is operative in several species of moths where post-coital pheromonostasis has been observed. Sperm quality is not important for pheromonostasis in H. virescens, because males with apyrene or eupyrene sperm elicit similar pheromonostatic responses. The pheromonostatic activity of the ecdysteroid 20-OH-ecdysone appears to be the result of a direct effect on the sex pheromone glands. © 1996 Wiley-Liss, Inc.
Social exchange: Empirical examination of form and focus

Abstract We investigate similarities and differences among prominent types of social exchange (psychological contract fulfillment, perceived organizational support, trust in the organization, leader-member exchange, and trust in the supervisor) and propose that two higher-order factors represent social exchanges with the organization and with the supervisor . We investigate their prediction of important employee work attitudes, citizenship behaviors, and performance. Based on data from 448 employees, empirical tests support the existence of organization- and supervisor-directed social exchanges. Tests using structural equation modeling support unique predictions of attitudinal and behavioral work outcomes.
Challenges in the use of density functional theory to examine catalysis by M-doped ceria surfaces

For CeO2 or M-doped CeO2 catalysts, reliable energetics associated with surface reactivity requires accurate representation of oxidized and reduced metal states. Density functional theory (DFT) is used extensively for metals and metal oxides; however, for strongly correlated electron materials, conventional DFT fails to predict both qualitative and quantitative properties. This is the result of a localized electron self-interaction error that is inherit to DFT. DFT+U has shown promise in correcting energetic errors due to the self-interaction error, however, its transferability across processes relevant to surface catalysis remains unclear. Hybrid functionals, such as HSE06, can also be used to correct this self-interaction error. These hybrid functionals are computationally intensive, and especially demanding for periodic surface slab models. This perspective details the challenges in representing the energetics of M-doped ceria catalyzed processes and examines using DFT extensions to model the localized electronic properties. © 2013 Wiley Periodicals, Inc.
Astrocyte Progression from G1 to S Phase of the Cell Cycle Depends upon Multiple Protein Interaction

The proliferation of cultured astrocytes is positively and negatively regulated, respectively, by the endogenous neuropeptides, endothelin-3 (ET-3) and atrial natriuretic peptide (ANP). Here, we determined the important steps for the modulation by ET and ANP of G1 to S phase cell cycle progression. ET-3 stimulated an increased number of fetal rat diencephalic astrocytes to progress through G1/S, and this was blocked significantly by ANP. ET augmented the gene expression and/or protein production of D-type, A and E cyclins, whereas ANP inhibited these events significantly. ET also stimulated the activation of the cyclin-dependent kinases Cdk2, Cdk4, and Cdk6, directed against the retinoblastoma protein pRb, and this was inhibited by as much as 80% by ANP. As an additional mechanism of cell cycle restraint, ANP stimulated the production of multiple cyclin-dependent kinase inhibitory (CKI) proteins, including p16, p27, and p57. This was critical because antisense oligonucleotides to each CKI reversed ANP-induced inhibition of ET-stimulated DNA synthesis by as much as 85%. CKI antisense oligonucleotides also reversed the ANP inhibition of Cdk phosphorylation of pRb. In turn, ET inhibited ANP-stimulated production of the CKIs, thereby promoting cell cycle progression. Specific and changing associations of the CKI with Cdk2 and Cdk4 were stimulated by ANP and inhibited by ET. Our findings identify several mechanisms by which endogenous modulators of astrocyte proliferation can control the G1-S progression and indicate that multiple CKIs are necessary to restrain cell cycle progression in these cells.
Bi-velocity hydrodynamics: Single-component fluids

Abstract Acceptance of the Navier–Stokes–Fourier (NSF) equations as the fundamental equations of single-component continuum fluid mechanics for liquids and gases is noted to be inseparably linked to Euler’s implicit, but unproved, hypothesis that but a single-velocity field is required to characterize the four physically different, context-specific, velocities appearing in the mass, momentum, and energy equations. To test Euler’s hypothesis, velocity is added to the usual list of quantities requiring constitutive formulation – namely the heat flux q and viscous stress T – in order to effect closure of the mass, momentum, and energy equations. Establishment of this enlarged set of constitutive relations is effected by using conventional linear irreversible thermodynamics (LIT) principles governing the behavior of simple fluid continua, importantly including satisfaction of Onsager reciprocity as a fundamental continuum requirement. The resulting analysis shows that, in general, two velocities rather than one are required and, concomitantly, that additional driving forces must be added to each of the standard constitutive equations for the Fourier’s-law heat flux q = − k ∇ T and the Newton’s-law viscous stress T = 2 η ∇ v m ¯ (wherein the “mass velocity” v m is the context-specific velocity appearing in the continuity equation ∂ρ / ∂t + ∇ · ( ρ v m ) = 0). For the particular case of dilute gaseous continua explicit expressions are established for the phenomenological coefficients appearing in these additional constitutive contributions. Determination of these coefficients is effected using data derived from the Chapman–Enskog–Burnett constitutive expressions for q and T , the latter obtained by solving the Boltzmann equation at small Knudsen numbers, including so-called rarefied-gas contributions. These coefficients are found to be nonzero, confirming the conclusion, inter alia , that two velocities are constitutively required to quantify hydrodynamic behavior for gases and, by inference, for liquids too. Collectively, these velocity, heat flux, and stress constitutive findings collectively negate the current belief that the NSF equations fully describe the physics of viscous fluid continua. Rather, they do so only in limiting cases where the additional constitutive terms than we have found necessary for completeness are asymptotically small.
Mechanism of stress-induced subsensitivity to norepinephrine

Abstract Chronic footshock stress in rats produces a persistent reduction in the sensitivity of the norepinephrine (NE)-cAMP generating system in the cerebral cortex, an effect similar to that reported after chronic antidepressant treatment. The present studies show that footshock-induced subsensitivity is not related to changes in either beta or alpha-1 adrenergic receptors, phosphodiesterase or total adenylate cyclase activity. The stress does induce a small, selective decrease in binding at high affinity alpha-2 receptor sites but this change does not appear to explain the decreased responsiveness to NE. These data and related findings by others using restraint stress indicate that the mechanism of subsensitivity after chronic stress resembles in part that seen after antidepressants but may also involve additional phenomena which may not occur after the latter agents.