cssi/SciSciGPT-SciSciNet huggingface dataset:
Biting the Hand that Heals You: Encounters with Problematic Patients in a General Veterinary Practice

This discussion focuses on veterinary practice as a form of service delivery. Based on data collected during a year of participant observation in a major veterinary hospital in the northeast, the paper examines the criteria veterinarians routinely used to define nonhuman patients as problematic and the means they employed to deal with troublesome animals. The conclusion frames veterinarians' tactics for evaluating and controlling patients within the larger context of how rule-breakers are identified in everyday interactional settings and the routine approaches used in the exercise of social control.
The Impact of the Temporal Variability of Seafloor Roughness on Synthetic Aperture Sonar Repeat–Pass Interferometry

In this paper, we review past work and present new analysis of the temporal variability of seafloor roughness and how this variability impacts synthetic aperture sonar (SAS) repeat-pass interferometry. The new work presented here uses a model based on first-order perturbation theory for acoustic interface scattering to link the complex coherence of SAS images taken at different times to the decorrelation of seafloor-roughness spectral estimates. Results are assessed through a comparison of decorrelation values generated by processing seafloor roughness data recorded by a digital photogrammetry system and complex SAS image data acquired with a translating source/receiver rail assembly. These data sets were collected on sandy seafloors off the western coast of Florida as part of the U.S. Office of Naval Research (ONR)-sponsored 2004 Sediment Acoustics Experiment (SAX04). Our results show that the diffusion model for changes in sediment roughness developed previously [ D. R. Jackson , IEEE J. Ocean. Eng., vol. 34, no. 4, pp. 407-422, Oct. 2009] provides an excellent fit to our data over a large range of spatial frequencies. In both the past work and new analysis, decorrelation was found to be frequency dependent with e-folding times (i.e., decay constants) of hours to days, setting a limit on reasonable time frames for successful repeat-pass coherent change detection.
E2 and E4 deformations in 232Th and 239,240,242Pu

Abstract Precise intrinsic quadropole and hexadecapole moments of 232 Th and 239,240,242 Pu have been determined from analysis of muonic K,L, and M X-rays. The quadropole and hexadecapole moments are in satisfactory agreement with both Hartree-Fock and shell-correction calculations. For 239 Pu, nine E2 matrix elements were independently determined. These E2 matrix elements are in good agreement with the adiabatic rotational model.
Us, Them and It: Modules, Genes, Environments and Evolution

Abstract: The Architecture of Mind is an ambitious and informative work, surveying an impressive range of empirical literature and arguing that the mind is massively modular. However, it suffers from two major theoretical flaws. First, Carruthers’ concept of a module is weak, so much so that it robs his thesis of massive modularity of any real substance. Second, his conception of how the mind’s modules evolved ignores the role of niche construction and cultural evolution to its detriment.
Airborne Measurements of Terrain-Induced Pressure Perturbations

Airborne measurement of the horizontal pressure field using differential GPS technology has been established during the last few years. Accurate aircraft measurement of the horizontalpressure gradientforce requires an independent determination of the height of the airborne platform above some reference level. Here the authors demonstrate a differential GPS technique that uses data from a fixed reference station to refine the vertical position of the aircraft. A series of research flight legs by the University of Wyoming King Air research aircraft (UWKA) were conducted during the winter seasons of 2008 and 2009 over the Medicine Bow Mountains in southern Wyoming. Flight patterns consisted of a series of geographically fixed, parallel legs along a quasi-isobaric surface above the mountainous terrain, allowing the finescale mapping of the horizontal pressure (or geopotential height) field. The removal of the large-scale gradient and tendency isolates the terrain-induced pressure perturbation field. Results obtained using differential GPS measurements of aircraft height show that the Medicine Bow Range induces pronounced horizontal pressure perturbations, with a leeside region of low pressure downwind of the crest, in two cases: on 11 February 2008 and 20 February 2009. A wind maximum is found downwind of the elevated terrain consistent with this pressure gradient. Simulations of these two cases were performed using the Weather Research and Forecasting Model (WRF). The WRF height patterns for the time of the UWKA flight matched the general isobaric height patterns observed. Simulations and observations consistently show that the cross-mountain acceleration is stronger when the perturbation pressure gradient is larger.
Corn production under three disk chisel depths

Although mulch-till represents 21% of the corn (Zea mays L.) acreage in the USA, limited research has addressed the question of optimum chisel dept. Farmer-operated studies were conducted in 1988 and 1989 in New York on excessively drained (loamy-skeletal, mixed, Typic Dystrochrept), well-drained (fine-loamy, mixed, mesic Glossoboric Hapludalf), and moderately well-drained (coarse-loamy, mixed, mesic Typic Fragiochrept) soils to evaluate the effet of spring chisel depth treatments at 5, 9, and 13 in. on surface residue, plant population, volumetric water content, and grain yield of corn (...)
Voyeur Nation? Changing Definitions of Voyeurism, 1950–2004

This boom in the vicarious is the hallmark of a people with not enough time on their hands, people who have a to-do list instead of a life, people for whom the download can never be quick enough. A...
Precipitating Factors in Asthma : Aspirin, Sulfites, and Other Drugs and Chemicals

Several types of reactions to drugs and chemicals may precipitate or perpetuate asthmatic relapse. This review focuses on reactions to aspirin and sulfites. Approximately 40 percent of patients with rhinosinusitis, nasal polyps, and asthma and 5 to 10 percent of all asthmatic patients are sensitive to apirin and aspirin-like nonsteroidal anti-inflammatory drugs at some time in their course. A prudent recommendation to all asthmatics is to substitute acetaminophen for aspirin. When aspirin/aspirin-like drug is essential for treatment of cardiovascular or musculoskeletal disorder, desensitization by cautious oral challenges with graded doses of aspirin can be accomplished. Treatment of the respiratory disorder per se by desensitization followed by daily therapeutic aspirin remains investigational. Sulfur dioxide and sulfites, commonly used as sanitizers and preservatives of foods and pharmaceuticals, may precipitate acute asthma in 5 percent or more of asthmatic patients. When the history suggests sulfite sensitivity, challenges can be used to confirm sensitivity and the patient counseled in avoidance of these chemicals.
A Case Study of an Emerging Community-Based Early Hearing Detection and Intervention Program: Part II. Team Building With Otolaryngologists and Pediatricians Using a Survey Approach

Purpose Physicians are vital team members of early hearing detection and intervention programs (EHDIPs), particularly in encouraging parents to comply with recommendations for follow-up services fo...
A Double-Blind, Multicenter, Parallel-Group Study of Paroxetine, Desipramine, or Placebo in Breast Cancer Patients (stages I, II, III, and IV) With Major Depression

Objective: This study compared the efficacy and safety of paroxetine and desipramine with those of placebo in the treatment of depressive disorders in adult women with breast cancer, stages I-IV. Method: In a double-blind, placebo-controlled study, 35 female outpatients with breast cancer and DSM-III-R major depression or adjustment disorder with depressed mood were randomly assigned to treatment with paroxetine (N = 13), desipramine (N = 11), or placebo (N = 11) for 6 weeks. Primary efficacy was assessed by change from baseline in score on the 21-item Hamilton Rating Scale for Depression (HAM-D), and the secondary outcome measure was change from baseline in the Clinical Global Impressions-Severity of Illness scale (CGI-S) score. Results: Mean changes in the total HAM-D and CGI-S scores from baseline to 6-week endpoint for the paroxetine and desipramine groups were not significantly different than those for the placebo-treated group. An unusually high rate of response (defined as > 50% improvement in the HAM-D score) in the placebo group was observed (55% [N = 6]); adverse events precipitated patient discontinuation in the active treatment groups (9% [N = 1] for desipramine, 15% [N = 2] for paroxetine) similar to that in the placebo-treated patients (18% [N = 2]). Improvement on symptom dimensions within the HAM-D and Hamilton Rating Scale for Anxiety (depressive, anxiety, cognitive, neurovegetative, or somatic) was also similar between groups. Conclusion: The small number of women in this study most likely contributed to the lack of observed differences in efficacy observed during the 6 weeks of treatment. Randomized, placebo-controlled trials of adequate power seeking to determine efficacy of antidepressants in the United States for the treatment of women with breast cancer and comorbid depression remain of paramount importance.
Soft computing for autonomous robotic systems

Abstract Neural networks (NN), genetic algorithms (GA), and genetic programming (GP) are augmented with fuzzy logic-based schemes to enhance artificial intelligence of automated systems. Such hybrid combinations exhibit added reasoning, adaptation, and learning ability. In this expository article, three dominant hybrid approaches to intelligent control are experimentally applied to address various robotic control issues which are currently under investigation at the NASA Center for Autonomous Control Engineering. The hybrid controllers consist of a hierarchical NN-fuzzy controller applied to a direct drive motor, a GA-fuzzy hierarchical controller applied to position control of a flexible robot link, and a GP-fuzzy behavior based controller applied to a mobile robot navigation task. Various strong characteristics of each of these hybrid combinations are discussed and utilized in these control architectures. The NN-fuzzy architecture takes advantage of NN for handling complex data patterns, the GA-fuzzy architecture utilizes the ability of GA to optimize parameters of membership functions for improved system response, and the GP-fuzzy architecture utilizes the symbolic manipulation capability of GP to evolve fuzzy rule-sets.
GENDER, RACE, AND THE DISTRIBUTION OF SOCIAL ASSISTANCE: Medicaid Use Among the Frail Elderly

Class-based theories of the welfare state suggest that welfare states stratify by social class, thus universal benefits are praised for fostering social equality and class solidarity whereas poverty-based benefits are criticized for fostering greater inequality and class conflict. Feminist theorists suggest that, in addition to social class, universal and poverty-based benefits are organized around dimensions of gender and race. I examine these arguments in conjunction with old-age reliance on Medicaid—the poverty-based long-term care system in the United States. Compared to white men, older Blacks, Hispanics, and women of all races have greater long-term care needs and fewer economic resources with which to meet those needs. Even when differences in income, education, age, marital status, and nursing home use are taken into account, gender and race are significantly related to Medicaid use. As Medicaid recipients, Blacks, Hispanics, and women of all races disproportionately face persistent poverty and di...
Induction of SV40 Early Transcription by Type I Interferon

Abstract Interferons (IFN) have cancer suppressor activities for many transformed cells; however, IFN does not suppress transformation by SV40 large T antigen. The studies described in this paper therefore evaluated the effect of IFN on SV40-promoted gene expression in 3T3T cells. The results show that SV40-promoted gene expression can be induced 200% or three-fold by Type I IFN treatment regardless of whether β-galactosidase or chloramphenical acetyltransferase (CAT) is used as the reporter gene. This IFN effect is dosage-dependent, requires 24-48 h of exposure for maximum induction of CAT activity, and is probably not due to a post-transcriptional effect of IFN on CAT because IFN has no effect on CAT expression driven by thymidine kinase promoter. The induction of SV40 early transcription by IFN does, however, require that the integration of plasmid within the cell's genome. Additional data specifically show that the SV40 promoter is required for IFN's effect because IFN will not induce CAT if the SV40 enhancer is inserted upstream of thymidine kinase promoter to control expression of CAT gene.
Application of the CMT algorithm to analog recordings of deep earthquakes

Abstract The distribution and characteristics of deep earthquakes provide important information on both the large-scale aspects of mantle convection as well as on the small-scale mechanics of apparent shear failure within descending lithospheric plates at large confining pressures. Neither of these processes is well understood, but the detailed knowledge of the spatial and temporal distribution of earthquakes, as well as the focal geometries, scalar moments, and details of the earthquake rupture process, provides constraints which can be used to differentiate between competing models of mantle circulation and theories of deep seismic rupture. With the objective of expanding and improving the database of source parameters for deep earthquakes, we evaluate the feasibility of applying the Harvard centroid moment tensor (CMT) algorithm to earlier (pre-1977) earthquakes recorded on seismographs with analog recording. Abundant records from the World Wide Standardized Seismograph Network (WWSSN) are available for events after 1962, and the data from these high-quality stations with a known standard response are easily digitized and subjected to analysis by the CMT algorithm. For earlier events, no standardized network of seismometers is available. Using a modem deep earthquake as a test case, we show that reliable single-station moment tensor solutions can be obtained from the Press-Ewing instrument at Pasadena. We apply the single-station technique to three historical earthquakes recorded on different types of electromagnetic and mechanical seismographs: the 1957 Java earthquake (Press-Ewing); the 1922 Peru earthquake (Wiechert); and the 1911 Peru-Brazil earthquake (Galitzin). Robust results can be achieved from these data provided the instruments are well calibrated, and an analysis of selected earlier deep earthquakes may quickly double or triple the time span of the database of deep earthquake source parameters.
Interferon-γ Upregulates CCR5 Expression in Cord and Adult Blood Mononuclear Phagocytes ♦ 1390

Interferon-γ Upregulates CCR5 Expression in Cord and Adult Blood Mononuclear Phagocytes ♦ 1390
Sites of Regulated Phosphorylation that Control K-Cl Cotransporter Activity

Modulation of intracellular chloride concentration ([Cl−]i) plays a fundamental role in cell volume regulation and neuronal response to GABA. Cl− exit via K-Cl cotransporters (KCCs) is a major determinant of [Cl−]I; however, mechanisms governing KCC activities are poorly understood. We identified two sites in KCC3 that are rapidly dephosphorylated in hypotonic conditions in cultured cells and human red blood cells in parallel with increased transport activity. Alanine substitutions at these sites result in constitutively active cotransport. These sites are highly phosphorylated in plasma membrane KCC3 in isotonic conditions, suggesting that dephosphorylation increases KCC3's intrinsic transport activity. Reduction of WNK1 expression via RNA interference reduces phosphorylation at these sites. Homologous sites are phosphorylated in all human KCCs. KCC2 is partially phosphorylated in neonatal mouse brain and dephosphorylated in parallel with KCC2 activation. These findings provide insight into regulation of [Cl−]i and have implications for control of cell volume and neuronal function.
Clinicopathologic findings in a dog with a retrobulbar meningioma

An 11-year-old Fox Terrier dog was evaluated for a 10-month history of progressive exophthalmia and visual deficits in the right eye. Ophthalmologic examination revealed severe corneal fibrosis and pigmentation, which obscured examination of the anterior chamber of the right eye. There was decreased retropulsion of the right eye. Neurological examination revealed an absent menace response bilaterally. Pupillary light reflex was normal in the left eye. Due to the corneal pathology, pupillary light reflex was unable to be evaluated in the right eye. A retrobulbar mass with heterogeneous echotexture was identified using ultrasonography. Cytological evaluation of a fine-needle aspirate of the mass disclosed a neoplastic cell population consisting of round to polygonal cells with lightly basophilic to gray cytoplasm and round to ovoid nuclei having a coarse granular chromatin pattern. Magnetic resonance imaging disclosed a right-sided retrobulbar mass that extended through the optic canal and was contiguous with an extra-axial mass in the ventral right rostral and middle cranial fossae. The mass displayed homogenous and strong contrast enhancement. Following exenteration, histological examination of the retrobulbar mass was consistent with meningioma. Immunohistochemically, tumor cells stained positive for vimentin (cytoplasmic) and E-cadherin (membranous), and negative for S100, pancytokeratin, and cytokeratins AE1 and AE3.
Role of Calpain‐ and Interleukin‐1β Converting Enzyme‐Like Proteases in the β‐Amyloid‐Induced Death of Rat Hippocampal Neurons in Culture

We investigated the potential role of different proteases in the death of cultured rat hippocampal pyramidal neurons induced by beta-amyloid (A beta) (25-35). Both A beta(25-35)- and staurosporine-induced death of these neurons appeared to involve apoptosis, as indicated using Hoechst 33342 and terminal dUDP nick end labeling staining, whereas NMDA-induced death appeared more complex. Two irreversible inhibitors of the interleukin-1 beta converting enzyme (ICE) and related proteases, Z-Val-Ala-Asp-CH2F and acetyl-Tyr-Val-Ala-Asp-chloromethyl ketone, blocked neuronal death produced by A beta(25-35), staurosporine, and NMDA to differing extents. Furthermore, MDL 28,170, a selective inhibitor of the calcium-regulated protease calpain, also inhibited death induced by all agents. A beta(25-35) and staurosporine stimulated the breakdown of the protein spectrin, a calpain substrate. Spectrin breakdown was inhibited by MDL 28,170 but not by ICE inhibitors. Leupeptin was only effective in preventing NMDA-induced death. These results support the role of apoptosis in neuronal death due to A beta(25-35) treatment and also suggest a role for calcium-regulated proteases in this process.
Cache-aware compositional analysis of real-time multicore virtualization platforms

Multicore processors are becoming ubiquitous, and it is becoming increasingly common to run multiple real-time systems on a shared multicore platform. While this trend helps to reduce cost and to increase performance, it also makes it more challenging to achieve timing guarantees and functional isolation. One approach to achieving functional isolation is to use virtualization. However, virtualization also introduces many challenges to the multicore timing analysis; for instance, the overhead due to cache misses becomes harder to predict, since it depends not only on the direct interference between tasks but also on the indirect interference between virtual processors and the tasks executing on them. In this paper, we present a cache-aware compositional analysis technique that can be used to ensure timing guarantees of components scheduled on a multicore virtualization platform. Our technique improves on previous multicore compositional analyses by accounting for the cache-related overhead in the components' interfaces, and it addresses the new virtualization-specific challenges in the overhead analysis. To demonstrate the utility of our technique, we report results from an extensive evaluation based on randomly generated workloads.
Sparsity-Promoting Extended Kalman Filtering for Target Tracking in Wireless Sensor Networks

In this letter, we study the problem of target tracking based on energy readings of sensors. We minimize the estimation error by using an extended Kalman filter (EKF). The Kalman gain matrix is obtained as the solution to an optimization problem in which a sparsity-promoting penalty function is added to the objective. The added term penalizes the number of nonzero columns of the Kalman gain matrix, which corresponds to the number of active sensors. By using a sparse Kalman gain matrix only a few sensors send their measurements to the fusion center, thereby saving energy. Simulation results show that an EKF with a sparse Kalman gain matrix can achieve tracking performance that is very close to that of the classical EKF, where all sensors transmit to the fusion center.
Developing a SSE-CMM-based security risk assessment process for patient-centered healthcare systems

Information security and privacy are the major concerns in healthcare domain. However, there lacks a comprehensive framework for evaluating the security engineering practices for healthcare systems. Current transition from institution-centered to patient-centered healthcare introduces additional security and privacy problems. With the intensive human (especially the patient) interaction involved in the patient-centered health care systems, information security and privacy can be assured not only by technologies and infrastructure but also by process. This paper develops a mapping from SSE-CMM process areas to the patient-centered healthcare domain aiming at establishing a set of metrics to assess security risks for patient-centered healthcare systems. Based on the mapping, a security risk assessment process is then proposed to evaluate the PHR system (a typical patient-centered healthcare system).
Spirituality in Death-Related Literature for Children

Elsewhere (see “Bereavement, Grief, and Mourning in Death-Related Literature for Children” in this special issue) I have explained that as I prepared a series of annotated bibliographies on death-r...
THE DOUBLY OBSTRUCTIVE HYPERTROPHIC CARDIOMYOPATHY

Hypertrophic cardiomyopathy (HCM) often results in mid-systolic left ventricular outflow tract (LVOT) obstruction secondary to basal septal hypertrophy and systolic anterior motion of the mitral valve. However, other etiologies of LVOT obstruction such as subaortic stenosis may also coexist. A 68
Development of a Portable Integrating Sphere Source for the Earth Observing System's Calibration Validation Programme

We have designed and built a portable integrating sphere source for use at the National Aeronautics and Space Administration (NASA) satellite sensor calibration facilities in support of the Earth Observing System (EOS) calibration programme. The source is designed to complement existing detector-based validation methodologies over the spectral range 400-2500 nm, affording extra flexibility in implementing the programme. Details of the design and operation of the portable source will be described and discussed.
Fermi-Segrè Formula

A derivation of the nonrelativistic Fermi-Segr\`e formula for the probability of finding a valence $s$-electron at the nucleus of an atom in terms of the energy eigenvalues of the electron is presented which makes use of the effective-range method drawn from scattering theory and a refinement of the JBWK method which avoids problems with the Coulomb singularity of the ion core potential.
Redesign solution for civicinfo bc web site

According to the mission statement on the home page, CivicInfo BC is 'a web-based resource the main goal of which is to facilitate information sharing and collaboration among people who work, or have an interest in the British Columbia local government sector. Rob MacDonald, Marcia Peterson, and Alan Rosenthal conducted a Contextual Inquiry of the CivicInfo BC Web site at the District of North Vancouver and the District of West Vancouver municipal government offices. At the conclusion of the interview, we created an Affinity Diagram to analyze the issues that we observed.After performing an analysis of the tasks conducted by the users that we observed during the contextual inquiry, in addition to the context in which they are performed, we conducted a scenario-based usability study in which participants were given a set of tasks to complete for each of our proposed redesigns of the CivicInfo BC Web site. Users were asked to "think aloud" while working through each task. The purpose of the think aloud method is to gain an understanding of the participants thought processes, expectations, and how they came to make their decisions.The study was conducted by Alan Rosenthal using Microsoft Live Meeting. The use of Live Meeting enabled Marcia Peterson and Rob MacDonald to participate remotely in the usability study via conference call. Screen activity was also recorded using Camtasia Recorder.
Measurements of off-peak spectral absorption coefficients (in CH2O) for an isolated Voigt line☆

Abstract We describe the measurement of an off-peak spectral absorption coefficient for an isolated spectral line using a laser light source. This type of experiment may be used to determine the following line parameters: the line strength (S), the collision-broadened half-widths for self-broadening (b0c,F and for inert-gas broadening (b0c, I) per unit pressure, and the displacement of the laser frequency from the line center (Δω). The theoretical relations have been applied to absorption measurements on formaldehyde using an HeXe laser light source at 3.508 μ.
Molecular self-diffusion in nanoscale cylindrical pores and classical Fick's law predictions.

Molecular-dynamics calculations are carried out to study the self-diffusion of water molecules confined in cylindrical pores. It is found that the classical Fick’s law description provides a surprisingly accurate prediction for the general behaviors of self-diffusion even for pore size of a few molecular diameters. The diffusion coefficient in the axial direction is reduced relative to bulk fluids for pore size less than about ten molecular diameters. In the radial direction, the mean-square displacement accurately follows Fick’s law prediction, but with an average diffusion coefficient slightly lower than the bulk value. The origin of the diffusion behaviors is traced to the molecular motion in the restricted geometry of the cylindrical pores.
Studies on Inc-P plasmids in Erwinia carotovora subsp. carotovora

Inc-P plasmids, RP4, R751, pMO850, and pRK2013 were transferred to Erwinia carotovora. These plasmids were stably maintained in E. carotovora and the transconjugants were efficient donors of respective plasmids to other strains of E. carotovora and Escherichia coli. These plasmids were not able to mobilize chromosomal markers from one strain of E. carotovora to another strain of E. carotovora even in the presence of homologous DNA sequences on the plasmid and the bacterial chromosome. The presence of Inc-P plasmid does not affect the pathogenic phenotype of E. carotovora. A broad host range Inc-P cosmid, pLAFR1, was transferred to E. carotovora with the help of pRK2013, suggesting the potential use of a binary plasmid system for genetic complementation in E. carotovora.
A New Method of Depositing Amorphous Hydrogenated Silicon Carbide with Low Ir-Detected Microstructure

We report a new method of depositing amorphous hydrogenated silicon carbide thin films with low IR-detected microstructure in a plasma-enhanced chemical vapor deposition reactor. Films prepared at various conditions are studied with Fourier-transform infrared absorption. Their optical band gaps and photoconductivities are also measured. The amount of microstructure can be controlled by adjusting the powered-electrode potential during deposition, and the microstructural changes are reflected in the film properties. By applying an external dc voltage to the rf-excited powered electrode, we can shift the optimal deposition temperature from 250 °C to as low as 100 °C. We find that films deposited at positive powered-electrode potential and low substrate temperature exhibit less microstructure, wider optical band gaps, and faster deposition rates than films deposited at conventional conditions.
Robust Control and Time-Domain Specifications for Systems of Delay Differential Equations via Eigenvalue Assignment

An approach to eigenvalue assignment for systems of linear time-invariant (LTI) delay differential equations (DDEs), based upon the solution in terms of the matrix Lambert W function, is applied to the problem of robust control design for perturbed LTI systems of DDEs, and to the problem of time-domain response specifications. Robust stability of the closed-loop system can be achieved through eigenvalue assignment combined with the real stability radius concept. For a LTI system of DDEs with a single delay, which has an infinite number of eigenvalues, the recently developed Lambert W function-based approach is used to assign a dominant subset of them, which has not been previously feasible. Also, an approach to time-domain specifications for the transient response of systems of DDEs is developed in a way similar to systems of ordinary differential equations using the Lambert W function-based approach.
Interaction between DNA Polymerase λ and Anticancer Nucleoside Analogs

The anticancer activity of cytarabine (AraC) and gemcitabine (dFdC) is thought to result from chain termination after incorporation into DNA. To investigate their incorporation into DNA at atomic level resolution, we present crystal structures of human DNA polymerase λ (Pol λ) bound to gapped DNA and containing either AraC or dFdC paired opposite template dG. These structures reveal that AraC and dFdC can bind within the nascent base pair binding pocket of Pol λ. Although the conformation of the ribose of AraCTP is similar to that of normal dCTP, the conformation of dFdCTP is significantly different. Consistent with these structures, Pol λ efficiently incorporates AraCTP but not dFdCTP. The data are consistent with the possibility that Pol λ could modulate the cytotoxic effect of AraC.
Apical localization of ITPK1 enhances its ability to be a modifier gene product in a murine tracheal cell model of cystic fibrosis

A new aspect of research into the pathogenesis of cystic fibrosis (CF) is a genetics-based search for ;modifier genes' that may affect the severity of CF lung disease. Using an alternative, cell biological approach, we show that ITPK1 should be considered a modifier gene. ITPK1 synthesizes an intracellular signal, inositol (3,4,5,6)-tetrakisphosphate [Ins(3,4,5,6)P4]. A bio-activatable, cell-permeable analogue of Ins(3,4,5,6)P4 inhibited Ca2+-dependent secretion of Cl- from polarized monolayers of immortalized mouse tracheal epithelial cells (MTEs). Analysis by high-pressure liquid chromatography showed endogenous Ins(3,4,5,6)P4 levels in CF MTEs were approximately 60% below those in wild-type MTEs (P<0.03). This adaptation, which improves purinergic activation of Ca2+-dependent Cl- secretion in CF MTEs, was exceptionally specific; there was no effect upon the cellular levels of all the other inositol phosphate signals. Real-time PCR provided the explanation: the level of ITPK1 expression in wild-type MTEs was twice as high as that in CF MTEs (P<0.002). The biological impact of this differential gene expression is amplified by ITPK1 being concentrated at the apical membrane of MTEs, which we discovered following confocal immunofluorescence microscopy. Compartmentalization of Ins(3,4,5,6)P4 synthesis adjacent to its site of action will enhance its regulatory capacity.
Preoperative autologous blood donation for oral and maxillofacial surgery: an analysis of 913 patients

Purpose Autologous transfusions are frequently used with elective surgical procedures and are a mandated choice under California law. Because unused units cannot be transfused to other patients, it is important to assess utilization and minimize waste. Methods The transfusion needs of 913 consecutive patients scheduled for major oral and maxillofacial surgery at the University of California San Francisco were evaluated in 3 categories: oncologic and reconstructive surgery (563), orthognathic surgery (260), and temporomandibular joint surgery (90). Results 24.9% of patients chose to undergo preoperative autologous blood donation. 24.2%, 20.6%, and 11.4% of oncologic and reconstructive surgery, orthognathic surgery, and temporomandibular joint surgery patients, respectively, who made an autologous donation preoperatively, subsequently received a transfusion postoperatively. Conclusion Transfusion needs for most oral surgery procedures are clearly overestimated; the relatively low risk of blood loss associated with these procedures today should be taken into account when asking patients to participate in preoperative autologous blood donation.
Economic definition of continuous fermentation goals

A cost analysis of the continuous fermentation of penicillin G shows that materials cost and product yields are more significant than throughput rate. Number of fermentation stages, productivity, and the implications for research and development are discussed.
Prognostic implications of serial 18-fluoro-deoxyglucose emission tomography in multiple myeloma treated with total therapy 3

Prognostic implications of 3 imaging tools, metastatic bone survey, magnetic resonance imaging, and positron emission tomography (PET), were evaluated in 2 consecutive Total Therapy 3 trials for newly diagnosed myeloma. Data including PET at baseline and on day 7 of induction as well as standard prognostic factors were available in 302 patients of whom 277 also had gene expression profiling (GEP)-derived risk information. According to multivariate analysis, more than 3 focal lesions on day 7 imparted inferior overall survival and progression-free survival, overall and in the subset with GEP-risk data. GEP high-risk designation retained independent significance for all 3 end points examined. Thus, the presence of > 3 focal lesions on day 7 PET follow-up may be exploited toward early therapy change, especially for the 15% of patients with GEP-defined high-risk disease with a median overall survival expectation of 2 years. This trial was registered at www.clinicaltrials.gov as #NCT00081939 and # NCT00572169.
Guest Editorial — Developmental Studies of Twins from Birth on: Heredity, Environment, Biomedical Variables, and Co-twin Relations

The reports in this section demonstrate several ways in which longitudinal research with twins is informative for the study of development. All of these twins have been followed for long time periods. These results are the latest stage of study for each. By virtue of their long-term nature, together these studies provide information on patterns and changes in several developmental areas from infancy to adulthood. They also document when specific variables no longer exert any influence on development. The first report, by Alin Akerman and Suurvee (“The Cognitive and Identity Development of Twins at 16 Years of Age: A Follow-up Study of 32 Twin Pairs”) is a study of twins followed from birth to 16 years of age. The second report, by Ebeling, Porkka, Penninkilampi-Kerola, Berg, Jarvi, and Moilanen (“Inter-twin Relationships and Mental Health”), is a study of twins followed from pregnancy to 22–30 years of age. The third report, by Lange (“Coping Ability at Midlife in Relation to Genetic and Environmental Influences at Adolescence”), is a study of twins and singletons followed from 10 to 16 years of age to 35 years of age. The section attests to the perseverance of these authors as researchers, and to the strength of the personal relationships of these authors with the individuals in their projects.
An integrated plasma equipment-feature scale model for ionized metal physical vapor deposition

Summary form only given. Ionized metal physical vapor deposition (IMPVD) is used to deposit diffusion barriers and metal seed layers into high aspect ratio trenches for interconnect wiring in the fabrication of microelectronics devices. To decrease the RC time delay of signals, Cu interconnects are replacing Al whose resistance is almost twice that of Cu. To improve the design of IMPVD systems, it is useful to have a comprehensive simulator. To address this need, an integrated plasma equipment-feature model has been developed, and applied to the investigation of Cu IMPVD. The computational tools use in this study are the two-dimensional Hybrid Plasma Equipment Model (HPEM), the Plasma Chemistry Monte Carlo Simulation (PCMCS) and the Monte Carlo feature profile model (MCFPIM). The HPEM produces species densities and source functions in the bulk plasma. The PCMCS computes the trajectories of ions and neutral species which are incident onto features based on the species densities and sources from the HPEM. The MCFPM uses these fluxes to simulate the deposition profile in a trench. The MCFPM, originally written for etching, was extended to deposition by adding surface diffusion algorithms. These algorithms use Monte Carlo techniques to move adsorbed pseudoparticles on the surface employing probabilities based on the local inter-particle potentials.
Structure of a one-component plasma in an external field: A molecular-dynamics study of particle arrangement in a heavy-ion storage ring.

A one-component plasma has been studied by molecular dynamics calculations to simulate the behavior of charged particles in heavy-ion storage rings. The Hamiltonian used confines the plasma in the directions lateral to the direction of travel in the ring in the frame of reference which is moving with the beam. The results show an unexpected stratification of density in the lateral direction, and a tendency towards a first-neighbor coordination of 14(8+6) seems incipient. On each shell we observe a triangular pattern of particle arrangement.
Nonlinear optical properties of noble metals at the interband transition threshold

We report measurements of the cubic optical susceptibility of copper at the interband transition threshold. Both real and imaginary parts of the susceptibility are determined from nonlinear transmission and reflection experiments with a copper/silica composite sample irradiated by picosecond laser pulses.
Improvement in vision: a new goal for treatment of hereditary retinal degenerations

Introduction: Inherited retinal degenerations (IRDs) have long been considered untreatable and incurable. Recently, one form of early-onset autosomal recessive IRD, Leber congenital amaurosis (LCA) caused by mutations in RPE65 (retinal pigment epithelium-specific protein 65 kDa) gene, has responded with some improvement of vision to gene augmentation therapy and oral retinoid administration. This early success now requires refinement of such therapeutics to fully realize the impact of these major scientific and clinical advances. Areas covered: Progress toward human therapy for RPE65-LCA is detailed from the understanding of molecular mechanisms to preclinical proof-of-concept research to clinical trials. Unexpected positive and complicating results in the patients receiving treatment are explained. Logical next steps to advance the clinical value of the therapeutics are suggested. Expert opinion: The first molecularly based early-phase therapies for an IRD are remarkably successful in that vision has improved and adverse events are mainly associated with surgical delivery to the subretinal space. Yet, there are features of the gene augmentation therapeutic response, such as slowed kinetics of night vision, lack of foveal cone function improvement and relentlessly progressive retinal degeneration despite therapy, that still require research attention.
Hospital variation and risk factors for bronchopulmonary dysplasia in a population-based cohort.

Importance Bronchopulmonary dysplasia (BPD) remains a serious morbidity in very low-birth-weight (VLBW) infants ( Objective To identify individual risk factors for BPD development and hospital variation of BPD rates across all levels of neonatal intensive care units (NICUs) within the California Perinatal Quality Care Collaborative. Design, Setting, and Participants Retrospective cohort study (January 2007 to December 2011) from the California Perinatal Quality Care Collaborative including more than 90% of California’s NICUs. Eligible VLBW infants born between 22 to 29 weeks’ gestational age. Exposures Varying levels of intensive care. Main Outcomes and Measures Bronchopulmonary dysplasia was defined as continuous supplemental oxygen use at 36 weeks’ postmenstrual age. A combined outcome of BPD or mortality prior to 36 weeks was used. Multivariable logistic regression accounting for hospital as a random effect and gestational age as a risk factor was used to assess individual risk factors for BPD. This model was applied to determine risk-adjusted rates of BPD across hospitals and assess associations between levels of care and BPD rates. Results The study cohort included 15 779 infants, of which 1534 infants died prior to 36 weeks’ postmenstrual age. A total of 7081 infants, or 44.8%, met the primary outcome of BPD or death prior to 36 weeks. Combined BPD or death rates across 116 NICUs varied from 17.7% to 73.4% (interquartile range, 38.7%-54.1%). Compared with level IV NICUs, the risk for developing BPD was higher for level II NICUs (odds ratio, 1.23; 95% CI, 1.02-1.49) and similar for level III NICUs (odds ratio, 1.04; 95% CI, 0.95-1.14). Conclusions and Relevance Bronchopulmonary dysplasia or death prior to 36 weeks’ postmenstrual age affects approximately 45% of VLBW infants across California. The wide variability in BPD occurrence across hospitals could offer insights into potential risk or preventive factors. Additionally, our findings suggest that increased regionalization of NICU care may reduce BPD among VLBW infants.
Pim kinase inhibitors sensitize prostate cancer cells to apoptosis triggered by Bcl-2 family inhibitor ABT-737

Pim serine/threonine kinases contribute to prostate tumorigenesis and therapeutic resistance, yet Pim kinase inhibitors seem to have only limited effects on prostate cancer cell survival. Because overexpression of Bcl-2 family members are implicated in chemotherapeutic resistance in prostate cancer, we investigated the cooperative effects of Pim kinase inhibition with ABT-737, a small molecule antagonist of Bcl-2 family members. Strikingly, the addition of ABT-737 to Pim inhibitors triggered a robust apoptosis of prostate cancer cells in vitro and in vivo. Pim inhibitors decreased levels of the Bcl-2 family member Mcl-1, both by blocking 5′-cap dependent translation and decreasing protein half life. In addition, Pim inhibition transcriptionally increased levels of the BH3 protein Noxa by activating the unfolded protein response (UPR), lead to eIF-2α phosphorylation and increased expression of CHOP. Increased levels of Noxa also inactivated the remaining levels of Mcl-1 protein activity. Notably, these specific protein changes were essential to the apoptotic process because ABT-737 did not inhibit Mcl-1 protein activity and Mcl-1 overexpression blocked the apoptotic activity of ABT-737. Our results therefore suggest that this combination treatment could be developed as a potential therapy for human prostate cancer where overexpression of Pim kinases and antiapoptotic Bcl-2 family members drives tumor cell resistance to current anticancer therapies. Cancer Res; 72(1); 294–303. ©2011 AACR.
Cohabitation and the Future: Guaranteed Survival?

In cases of fission, on Lewis' account, distinct individuals share stages prior to fission. There is a sense in which the survival of such 'cohabiting' individuals is guaranteed. Had fission not occurred there would have been a single individual in their place. So if they, those cohabiting individuals, exist they must survive fission. To that extent any concern they might have about whether they will survive fission is unwarranted. But only to that extent. Like cohabitants, we singles are also guaranteed that our lives won't be over until they're over. Singles and cohabitants have the same reason to be sanguine about their futures—and the same reason to be concerned.
The imprisoned nonviolent drug offender: Specialized martyr or versatile career criminal?

Some observers oppose imprisoning nonviolent drug offenders because they view incarceration as costly and such persons as generally benign. The careercriminal literature has established that perpetrators, including drug violators, commit an array of offenses. The current study merges these debates using a sample of 500 arrested adults selected from an urban jail in the western United States. Drug offenders amassed a much more extensive arrest history than other suspects net the effects of age, race, sex, prison history, and arrest onset. Drug offenders are quite versatile and do not conform to the image of specialized violators who are nominally criminal.
Input Summation by Cultured Pyramidal Neurons Is Linear and Position-Independent

The role of dendritic morphology in integration and processing of neuronal inputs is still unknown. Models based on passive cable theory suggest that dendrites serve to isolate synapses from one another. Because of decreases in driving force or resistance, two inputs onto the same dendrite would diminish their joint effect, resulting in sublinear summation. When on different dendrites, however, inputs would not interact and therefore would sum linearly. These predictions have not been rigorously tested experimentally. In addition, recent results indicate that dendrites have voltage-sensitive conductances and are not passive cables. To investigate input integration, we characterized the effects of dendritic morphology on the summation of subthreshold excitatory inputs on cultured hippocampal neurons with pyramidal morphologies. We used microiontophoresis of glutamate to systematically position inputs throughout the dendritic tree and tested the summation of two inputs by measuring their individual and joint effects. We find that summation was surprisingly linear regardless of input position. For small inputs, this linearity arose because no significant shunts or changes in driving force occurred and no voltage-dependent channels were opened. Larger inputs also added linearly, but this linearity was caused by balanced action of NMDA and IA potassium conductances. Therefore, active conductances can maintain, paradoxically, a linear input arithmetic. Furthermore, dendritic morphology does not interfere with this linearity, which may be essential for particular neuronal computations.
Price-Endings When Prices Signal Quality

This paper provides a theoretical explanation for why firms behave as though they use round prices to signal quality. By replacing the linear demand curve in Bagwell and Riordan's (1991) price as a signal of quality model with a kinked demand curve, and analyzing what price endings firms are most likely to use, the following observations can be made: (1) Firms that are using high prices to signal quality are more likely to set those prices at round numbers, and (2) price-endings themselves are not necessarily signals of quality. A simulation was conducted to demonstrate that these findings generally hold true even in the presence of demand spikes at 9-ending prices (e.g., Schindler and Kibarian 1996). Finally, empirical evidence is provided to demonstrate that firms tend to use more round prices for higherquality products, and that this relationship is even stronger for product categories where consumers are less able to detect the true level of quality prior to purchase.