cssi/SciSciGPT-SciSciNet huggingface dataset:
α-AP-2 Directs Myosin VI-dependent Endocytosis of Cystic Fibrosis Transmembrane Conductance Regulator Chloride Channels in the Intestine

The actin motor myosin VI regulates endocytosis of cystic fibrosis transmembrane conductance regulator (CFTR) in the intestine, but the endocytic adaptor linking CFTR to myosin VI is unknown. Dab2 (Disabled 2) is the binding partner for myosin VI, clathrin, and α-AP-2 and directs endocytosis of low density lipoprotein receptor family members by recognizing a phosphotyrosine-binding domain. However, CFTR does not possess a phosphotyrosine-binding domain. We examined whether α-AP-2 and/or Dab2 were binding partners for CFTR and the role of myosin VI in localizing endocytic adaptors in the intestine. CFTR co-localized with α-AP-2, Dab2, and myosin VI and was identified in a complex with all three endocytic proteins in the intestine. Apical CFTR was increased in the intestines of Dab-2 KO mice, suggesting its involvement in regulating surface CFTR. Glutathione S-transferase pulldown assays revealed binding of CFTR to α-AP-2 (but not Dab2) in the intestine, whereas Dab-2 interacted with α-AP-2. siRNA silencing of α-AP-2 in cells significantly reduced CFTR endocytosis, further supporting α-AP-2 as the direct binding partner for CFTR. α-AP-2 and Dab2 localized to the terminal web regions of enterocytes, but Dab2 accumulated in this location in Snell's Waltzer myosin VI(sv/sv) intestine. Ultrastructural examination revealed that the accumulation of Dab2 correlated with prominent involution and the loss of normal positioning of the intermicrovillar membranes that resulted in expansion of the terminal web region in myosin VI(sv/sv) enterocytes. The findings support α-AP-2 in directing myosin VI-dependent endocytosis of CFTR and a requirement for myosin VI in membrane invagination and coated pit formation in enterocytes.
Use of HIV health care in HIV-seropositive crack cocaine smokers and other active drug users.

PurposeWe assessed the use of HIV care among HIV-seropositive crack cocaine smokers and other active drug users in Miami-Dade County, FL. Methods Personal interviews were conducted with 327 adults recruited from inner city neighborhoods. Cross-tabulations and logistic modeling were used to analyze the relationship between selected variables and use of HIV care. Results One-third of respondents had not seen a provider for HIV-related health care in the past 12 months. Among those who had seen a provider, only 33.8% were receiving highly active antiretroviral therapy (HAART). Factors associated with utilization of HIV-related health care were age, race, having a usual source of care, health insurance, time elapsed since time of diagnosis, and reports of moderate to extreme interference of pain with daily activities. Implications These findings suggest the need to develop, implement, and evaluate intervention strategies to improve use of HIV medical care among active drug users.
A new model of renal microvascular endothelial injury

Although the importance of injury with consequent activation of endothelium is well-recognized in diseases affecting the glomerular endothelial cell (GEN), research on GEN injury in vivo has been hampered by the lack of adequate animal models. Here we report the establishment and characterization of a new GEN injury model in rats. This model was induced by selective renal artery perfusion with anti-GEN IgG and resulted in the severe acute renal failure with marked platelet deposition and development of a thrombotic microangiopathy involving glomeruli. Peritubular capillary endothelial cells were also damaged that was associated with severe tubular necrosis. Although the glomerular changes were severe, half of the glomeruli recovered by day 10, while interstitial changes remained throughout our observation time course. Proliferation of GEN was observed during the recovery phase. An increased expression of endothelial nitric oxide synthase in GEN was also observed, and may be an adaptive mechanism to counteract the thrombosis and ischemia. This model should be useful to investigate the pathophysiology of renal microvascular diseases and the mechanisms of GEN injury, activation and recovery in vivo.
A multiscale model applied to ionic polymer stiffness prediction

A multiscale modeling approach applied to the stiffness prediction of polymers with high cross-link density is discussed. The material of focus in this work is the ionic polymer Nafion®. The approach applies rotational isomeric state theory in combination with a Monte Carlo methodology to develop a simulation model for polymer chain conformation. From this a large number of end-to-end chain lengths between cross links are generated; the probability density function of these lengths is estimated with the most appropriate Johnson family method. This estimation is used in a Boltzmann statistical thermodynamics approach to the multiscale prediction of stiffness. This work addresses the importance of the simulated polymer chain length in the generation of stable predictions. The multiscale prediction is found to be physically reasonable; the approach has the potential of serving as a first-order prediction tool for properties that are experimentally difficult or impossible to measure.
Query Domains: Grouping Heterogeneous Sensors Based on Proximity

Efficient query processing in sensor networks involves identifying groups of nodes that coordinate to satisfy applications' requests. In this paper, we propose a query domain abstraction that allows an application to dynamically specify the nodes best suited to answering a particular query. To self-organize into such a coalition, nodes must satisfy a proximity function, a user-defined function that constrains the relative relationship among the group of nodes (e.g., based on a property of the network or physical environment or a logical property of the nodes). The proximity function removes the need to explicitly tag nodes with context information, and it provides a convenient mechanism for forming coalitions on-the-fly at query time. This facilitates the deployment of general-purpose sensor networks, where multiple applications can be run in the same network at the same time. In this paper, we model this abstraction, present a protocol to support the abstraction, and evaluate their performance.
Early Breakdown of Dendritic Bundles in the Retrosplenial Granular Cortex of Hypertensive Rats: Prevention by Antihypertensive Therapy

Layer II pyramidal neurons in retrosplenial granular cortex (Rg) give rise to apical dendrites that bundle together tightly in layer Ic and Ib and spread out in layer Ia, where they arborize extensively. These dendritic bundles in Rg become disorganized in very old rats. Since hypertensive rats appear to age more rapidly than normotensive rats, we tested the hypothesis that the disorganization of the dendritic bundles in layer I of Rg is present at a much earlier age in hypertensive rats [spontaneously hypertensive rats (SHR)] compared to normotensive rats [Sprague-Dawley rats (SD)]. Further, we tested the hypothesis that long-term, antihypertensive drug treatment (captopril) prevents or attenuates the breakdown of the dendritic bundles in Rg of SHR. The retrograde tracer Fluorogold was injected into Rg to document the morphology of the apical dendrites of the layer II Rg neurons. In 4-month-old SD and SHR, most densely labeled layer II neurons have labeled apical dendrites that are confined to the dendritic bundles in layer Ib and Ic, and these dendrites arborize extensively only in layer Ia of Rg. In 14-month-old SD this pattern is preserved, but in contrast, in 14-month-old SHR most of the labeled apical dendrites lie outside the bundles, and less than half these dendrites reach layer Ia. Chronic antihypertensive therapy significantly attenuates this disorganization in 14-month-old SHR. These data indicate that in SHR, the layer II neurons in Rg are highly vulnerable to the combined effects of hypertension and aging, and the results suggest that hypertension is a primary contributor to these structural alterations.
Generalized gradual channel modeling of field-effect transistors

The flow of current in the channel of the field-effect transistor (FET) is abstracted into a generalized curvilinear coordinate system that allows the transverse and longitudinal processes to be separated. By integrating over the conducting cross section of the channel, a set of generalized channel equations is derived that formally one-dimensionalizes the analysis of a FET for a Boltzmann balance equation transport model. Two mode approximations on the curvature of the channel and the uniformity of the velocity distribution across the channel allow the system of channel equations to be reduced to an extension of the gradual channel approximation of Schockley. The applicability of the formulation is demonstrated through the modeling of a GaAs metal-semiconductor FET (MESFET) that includes all of the Boltzmann equation terms for high-field electron transport as well as a small gate-length-to-channel-thickness ratio. The results indicate that gradual channel models, with suitable geometric modifications, can be used to study FETs using higher internal fields and smaller gate/channel dimensions than previously thought. >
Single-pass 3D lens rendering and spatiotemporal “Time Warp” example

This paper extends 3D lens techniques. Interactive 3D lenses, often called volumetric lenses, provide users with alternative views of datasets within spatially bounded regions of interest (focus) while maintaining the surrounding overview (context). In contrast to previous multi-pass rendering work, we discuss the strengths, limitations, and performance cost of a single-pass technique. For a substantial range of effects, it supports several interactive composable lenses at interactive frame rates without performance loss during increasing lens intersections or manipulations. Other cases, for which this performance cannot be achieved, are also discussed. Finally, we illustrate possible applications of our lens system, especially new Time Warp lenses for exploring time-varying datasets in interactive VR.
The impact of a pneumatic tube and computerized physician order management on laboratory turnaround time.

Study objective We assess the effect of sequential modifications in laboratory processing, including pneumatic tube transport and fully computerized order management, on laboratory turnaround time in the emergency department (ED). Methods This was an observational analysis of a comprehensive computerized database derived from ED, laboratory, and hospital information systems. The setting was an academic urban ED with annual census of 38,000. Participants and interventions included all patients who had laboratory testing (serum sodium level, troponin level, or CBC count) during three 1-month study periods: before pneumatic tube and computerized order management (prepneumatic tube), after pneumatic tube but before computerized order management (postpneumatic tube), and after both pneumatic tube and computerized order management (postpneumatic tube/computerized order management). The primary outcome measure was median laboratory turnaround time, reported with interquartile ranges. Additional measures included ED census and number of laboratory tests ordered during each study period. Results The monthly ED census was 3,021, 3,428, and 3,066 for the prepneumatic tube, postpneumatic tube, and postpneumatic tube/computerized order management periods. There was a significant decrease in turnaround time with each period and each test over time. For serum sodium testing, the median laboratory turnaround time decreased from 55.9 to 46.7 to 37.2 minutes for prepneumatic tube, postpneumatic tube, and postpneumatic tube/computerized order management periods. For CBC-count testing, median times decreased from 55.6 to 42.2 to 36.3 minutes, respectively. For troponin I testing, median times decreased from 52.8 to 41.8 to 30.6 minutes, respectively. Conclusion Changes in laboratory specimen management, including the use of a pneumatic tube and computerized order management, resulted in a progressive decrease in laboratory turnaround time in the study ED.
Abbreviation of systolic time intervals in acute mitral regurgitation: Effect of prosthetic mitral valve replacement

Systolic time intervals were measured in 26 patients with mitral regurgitation (acute in 14 and chronic in 12). In 13 of these patients (7 with acute and 6 with chronic mitral regurgitation) systolic time intervals were also measured after mitral valve replacement. Total electromechanical systole corrected for heart rate (Q-S2I) was of much shorter duration in the group with acute mitral regurgitation (472 ± 9 msec [mean ± standard error of the mean]) than in the group with chronic mitral regurgitation (516 ± 4.6 msec, P < 0.01). Before operation, the ratio of the preejection period (PEP) to left ventricular ejection time (LVET) and the angiographic ejection fraction did not differ in the groups with acute and chronic mitral regurgitation. The correlation between the PEPLVET ratio and ejection fraction was r = − 0.84, P < 0.01. Two weeks after operation, the PEPLVET ratio increased in all patients, but the increase was greater in those with lower preoperative values for this ratio. The mechanism of the early postoperative increase in the PEPLVET ratio is not clear, but serial studies performed over 6 months showed a return toward the preoperative value. It is concluded that preoperative systolic time intervals are useful for assessing left ventricular performance in all types of mitral regurgitation, but are especially useful for distinguishing between the acute and chronic varieties.
Determination of activation barriers for the diffusion of sodium through CIGS thin‐film solar cells

We have determined the activation energies of sodium diffusion from the soda-lime glass substrate through the Mo back-contact layer, as well as through copper indium gallium diselenide (CIGS) deposited on the Mo back-contact layer of CIGS thin-film solar cells. The activation energies were determined by X-ray photoelectron spectroscopy (XPS) to measure surface sodium concentrations before and after thermally induced diffusion. The activation energies were found to be similar for the diffusion of Na through the Mo/glass and CIGS/Mo/glass thin films, approximately 8.6 and 9.6kcal/mol, respectively. Furthermore, the sodium diffusion was found to occur by annealing in an environment of 1.0 × 10 -5 Torr of air, oxygen, or water vapor, but not in vacuum of less than 1 × 10 -8 Torr. In addition, the diffusion of Na was found to occur faster in the presence of oxygen than in water under identical annealing conditions.
From commune to household: statistics and the social construction of Chaianov's theory of peasant economy.

mands that some criterion (class, gender, age, profession, etc.) be used to reduce the number of variables examined. From the mid-nineteenth century-as statistics evolved from the simple "political arithmetic" of tax collectors and army recruiters into a potential science of human behavior-categorizing the population became a contentious issue that reflected the social and political agendas of data collectors. 1 At the same time, when data refused to be molded to researchers' assumptions, the task of putting people and their activities into analytical categories challenged the validity of the categories themselves. In this way, statistical representations and categories became socially constructed knowledge. Attempts by Russia's zemstvo statisticians to discover underlying "universal laws" of peasant society illustrate this tension in the process of collecting data and categorizing it for analysis.2 These attempts reflected researchers' assumptions and necessitated a shift in the way they perceived their subject. What began as investigations of the Russian peasant's repartitional land commune (mir or obshchina) soon shifted focus to individual peasant households. An examination of this process reveals the socially constructed nature of the household model of peasant economy offered in the work of A. V. Chaianov and others of the so-called Organization and Production School.3 On one hand, his approach to understanding the dynamics of the peasant economy differed sub
Evolutionary contrasts in insects: nutritional advantages of holometabolous development

ABSTRACT. Two insects, one holometabolous and one hemimetabolous, are compared and contrasted in respect to feeding efficiency, growth and respiration. An examination of cuticle production in these and other species leads to the conclusion that the nutritional burden of cuticle production in hemimetabolous forms has a significant effect on efficiency, and it is speculated that greater nutritional efficiency in holometabolous forms has been an important evolutionary advantage.
Optimal Observers for Decentralized Control

A method is developed for computing optimal observers for linear decentralized feedback control systems. Necessary conditions are derived for the decentralized output-feedback control to optimally approximate a given state-feedback control. The observer gains that satisfy the necessary conditions are found using a numerical gradient-type optimization. A control structure where decentralized observers share control-input information is also considered. For this structure, the optimal observers can be computed directly from a set of decoupled algebraic Riccati equations. Centralized control is treated as a special case, resulting in a simple and novel derivation of the known results for computing optimal centralized observers.
Two-Dimensional Imaging of Soot Volume Fraction in Pulsed Diffusion Flames by Laser-Induced Incandescence

Laser-Induced Incandescence (LII) is used in this study to measure soot volume fractions in steady and flickering ethylene diffusion flames burning at atmospheric pressure. Better understanding of flickering flame behavior also promises to improve understanding of turbulent combustion systems. A very-high-speed solenoid valve is used to force the fuel flow rate with frequencies between 10 Hz and 200 Hz with the same mean fuel flow rate of steady flame. Periodic flame flickers are captured by two-dimensional phase-locked emission and LII images for eight phases (0°–360°) covering each period. LII spectra scan for minimizing C2 swan band emission and broadband molecular florescence, a calibration procedure using extinction measurements, and corrections for laser extinction and LII signal trapping are carried out towards developing reliable LII for quantitative applications. A comparison between the steady and pulsed flames results and the effect of the oscillation frequency on soot volume fraction for the pulsed flames are presented.Copyright © 2006 by ASME
New Insight Into the Role of Enhanced Adrenergic Receptor-Effector Coupling in the Heart

The ability of the heart to augment the perfusion of vital organs and skeletal muscles during stress is predicated on its ability to increase contractility in response to adrenergic neurohormones that are released from postsynaptic nerve terminals within the heart and/or from the adrenal gland. These neurohormonal signals must then be detected and processed by a complex of proteins located within the sarcolemmal membrane, resulting in the conversion of the adrenergic signal to an alteration in the biomechanical properties of individual myocytes. This sarcolemmal protein complex consists of adrenergic receptors (ARs), guanine nucleotide–binding regulatory proteins, and the effector enzyme adenylyl cyclase. Myocardial contractility is augmented by the interaction of adrenergic agonists with β1- and/or β2-adrenergic receptors (βARs) located on the surface of the sarcolemmal membrane (see review in Reference 11 ). These 2 βAR subtypes are coupled to adenylyl cyclase activation by the stimulatory guanine nucleotide–binding protein (Gs). Interaction of the agonist-βAR complex with the heterotrimeric G protein catalyzes the release of GDP from the α-subunit of the G protein (αs), allowing the binding of GTP and the subsequent activation of adenylyl cyclase by αs-GTP. This activation persists until intrinsic GTPase activity of αs hydrolyzes the nucleotide, resulting in an inactive αs-GDP moiety.1 G-protein–mediated activation of adenylyl cyclase effects the synthesis of the intracellular second messenger cAMP and the resulting phosphorylation of a cAMP-dependent protein kinase (PKA). Once phosphorylated, PKA is then able to effect positive inotropic and chronotropic responses by phosphorylating a group of intracellular proteins, including phospholamban, and the L-type voltage-dependent calcium channel while at the same time enhancing lusitropy via alterations in the sensitivity of troponin for Ca2+. α-Subunits of some G proteins also appear to effect myocyte ion channel activity independent …
The Effect of Body Mass Index on Fluoroscopic Time and Radiation Dose During Sacroiliac Joint Injections

Abstract Background Sacroiliac joint (SIJ) injections are commonly performed under fluoroscopic guidance. Radiation exposure to patients and providers has not been comprehensively studied, particularly the effect of body mass index (BMI). Objective To identify whether patients with a larger BMI require longer fluoroscopy time or a larger radiation dose during performance of an SIJ injection. Design Retrospective study of an academic institution database. Setting Academic outpatient musculoskeletal clinic. Patients All patients who underwent SIJ injections during a 10-year period. Main Outcome Measurements Machine-reported fluoroscopic time and machine-reported radiation dose. A Bonferroni correction was implemented with P ≤ .01 as statistically significant. Results A total of 453 SIJ injections were performed in 359 patients. No statistically significant differences in fluoroscopy time were found between patients with BMI scores identified as normal, overweight, and obese ( P = .054). However, the radiation doses were significantly greater for patients with higher BMI scores (χ 2 [2, n=441] = 62.4, P 2 for normal weight, overweight, and obese patients, respectively. Although longer needles were used more often in obese patients (χ 2 [2, n=452] = 31.5, P P = .162). No relationships were identified between fluoroscopy time and first-time (as opposed to repeat) injection ( P = .123), trainee involvement (χ 2 [1, n=698] = 3.9, P = .049), or age ( P = .337). Conclusions Patients with an elevated BMI score who are undergoing SIJ injection receive an increased radiation dose despite equivalent fluoroscopic time. This finding suggests that the increased dose is likely due to x-ray output from the fluoroscope traversing a greater tissue mass, as opposed to the physician requiring more fluoroscopic images for proper needle placement. Fortunately, the increased radiation dose delivered to patients with a larger BMI score likely has negligible effects.
Solid state coordination chemistry of the oxovanadium-diphosphonate/copper-bipyrimidine system: Crystal structures of [{Cu2(bpyr)}VO(H2O)(HO3PCH2PO3)2] and [{Cu2(bpyr)}{Cu2(bpyr)(H2O)2}(VO2)2(HO3PCH2PO3)2(HO3PCH2PO3H)2]

Hydrothermal chemistry has been exploited in the preparation of two materials of the copper(II)-bipyrimidine/oxovanadium-organophosphonate family, the two dimensional [{Cu(bpyr)}VO(H 2 O)-(HO 3 PCH 2 PO 3 ) 2 ] (1) and the three-dimensional [{Cu 2 (bpyr)}[Cu 2 (bpyr)(H 2 O) 2 }(VO 2 ) 2 }(HO 3 PCH 2 PO 3 ) 2 -(HO 3 PCH 2 PO 3 H) 2 ]· 2H 2 0 (2 · 2H 2 0) (bpyr = 2,2'-bipyrimidine). The structure of 1 may be described as [{Cu 2 (bpyr)}(Cu 2 (bpyr)O 4 } 4n n · chains linked through {VO IV (H 2 O)(HO 3 PCH 2 PO 3 ) 2 } 4- units. In contrast, the structure of 2 consists of {Cu 2 (bpyr)} 2+ , {Cu 2 (bpyr)(H 2 O) 2 } 2+ and {V v O 2 (HO 3 PCH 2 PO 3 )-(HO 3 PCH 2 -P0 3 H)) 4 - subunits linked into a framework architecture. The vanadium component of the reaction mixture failed to incorporate into the two-dimensional structure of [{Cu(bpyr)(H 2 O 2 }{HO 3 PCH 2 CH 2 PO 3 H} 2 ](3). The architecture of 3 consists of'4+2' distorted octahedral Cu(II) sites linked through bpyr and diphosphonate ligands into a network. [Cu 2 (bpyr)Cl 2 ] (4) is a simple one-dimensional ribbon constructed from parallel {CuCl} n chains linked by bpyr ligands.
Behaviours of phoretic mites (Acari) associated with Ips pini and Ips grandicollis (Coleoptera: Curculionidae) during host‐tree colonization

Studies on interactions between bark beetles and phoretic mites have focused largely on dispersal life stages. However, many of these interactions occur within trees, where beetles and mites develop. Within-tree interactions are potentially important to beetle and mite reproduction, as well as beetle–mite phoretic pairings. We performed experiments aiming to characterize the behaviours of mites associated with Ips pini (Say) and Ips grandicollis (Eichoff) during nondispersal life stages. Mites are highly specific in the location on which they attach to beetles. Detachment from beetles is elicited by cues associated with both beetle vectors and tree hosts. Beetle condition can trigger rapid mite departure and Iponemus confusus Lindquist detach more rapidly from beetles colonizing tissue amended with the host tree secondary compound α-pinene than in un-amended tissue. Within-plant movement by detached mites is elicited by host plant volatiles. In olfactometer assays, Dendrolaelaps quadrisetus (Berlese) preferred volatiles from beetle-infested phloem over fresh phloem and blank controls. Within host plant tissue, fungal symbionts of beetles provide a resource for mites. Histiogaster arborsignis Berlese fed and reproduced more successfully on Pinus resinosa (Ait) phloem inoculated with the symbiotic fungus Ophiostoma ips (Rumbold) than on phloem with the opportunistic fungus Aspergillus fumigatus or blank controls.
Eyetracking reveals multiple-category use in induction

Category information is used to predict properties of new category members. When categorization is uncertain, people often rely on only one, most likely category to make predictions. Yet studies of perception and action often conclude that people combine multiple sources of information near-optimally. We present a perception-action analog of category-based induction using eye movements as a measure of prediction. The categories were objects of different shapes that moved in various directions. Experiment 1 found that people integrated information across categories in predicting object motion. The results of Experiment 2 suggest that the integration of information found in Experiment 1 were not a result of explicit strategies. Experiment 3 tested the role of explicit categorization, finding that making a categorization judgment, even an uncertain one, stopped people from using multiple categories in our eye-movement task. Experiment 4 found that induction was indeed based on category-level predictions rather than associations between object properties and directions. (PsycINFO Database Record
Abstract 1932: RNA-seq differential transcription analysis of TCGA colorectal cancer (CRC) transcriptomes reveals subtype-specific isoform usage

Background: Differential transcription analysis may reveal transcriptome aberrations associated with cancer progression and help identify important drivers in molecularly distinct subtypes of a disease. Methods: We developed a data-driven bioinformatics pipeline (DiffSplice) that performs differential transcription analysis at the alternative splicing (AS) level and allows accurate transcriptome reconstruction through joint analysis of all RNA-seq samples. In this study, we applied DiffSplice to RNA-seq data from TCGA CRC (n = 686) and evaluated the expression patterns of the detected AS events across the four consensus molecular subtypes (CMS) of the disease (n = 511): CMS1 - MSI Immune (hypermutated, n = 76); CMS2 - Canonical (epithelial, WNT/MYC activation, n = 220); CMS3 - Metabolic (epithelial, enriched for KRAS mutations, n = 72); and CMS4 - Mesenchymal (stromal invasion, TGFB activation, n = 143). Results: A total of 15,613 AS events were detected, including 5,128 events that involved novel splice junctions not cataloged in UCSC GAF2.0 transcriptome annotation. Exon skipping was the most common pattern with 6,482 occurrences, followed by 4,962 alternative splice sites, 2,689 alternative 5′/3′ transcription sites and 1,262 retained introns. In the subset of samples with CMS classification, a cross-subtype comparative analysis revealed 1,835 differentially transcribed loci from 1,634 genes, including 759 novel junctions (FDR Discussion: Here we present an in-depth transcriptome analysis of TCGA CRC data across the molecular subtypes of the disease. We were able to identify differential transcription patterns in an unbiased way by using a scalable and efficient computational approach that models both annotated and novel splice variants simultaneously. Our pipeline revealed a number of promising candidates that may be acting as key modulators in specific disease subsets and deserve further investigation. Citation Format: Yin Hu, Rodrigo Dienstmann, Justin Guinney. RNA-seq differential transcription analysis of TCGA colorectal cancer (CRC) transcriptomes reveals subtype-specific isoform usage. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1932. doi:10.1158/1538-7445.AM2015-1932
Flow Cytometric Screening for Selective Toxicity to Multidrug-Resistant Cells

Mixed cultures originally containing doxorubicin [(DOX) NCS-123127]-sensitive leukemia P388 (P388/S) cells and DOX-resistant leukemia P388 (P388/R) cells were treated with drugs for 1 hour or with radiation, grown until the cell numbers had increased 250 times (8 cell doublings), and incubated with 2 micrograms daunorubicin (NCS-82151)/ml for 1 hour. The fluorescence of intracellular anthracycline measured on a flow cytometer was used as a marker to distinguish P388/S and P388/R cells. The proportions of low-fluorescent P388/R cells and high-fluorescent P388/S cells were determined from fluorescence histograms. Selective toxicity for multidrug-resistant P388/R cells was indicated by the decreased proportion of these cells in the mixed cultures. In untreated cultures grown from suspensions containing equal proportions of P388/R and P388/S cells, the mean proportion of P388/R cells after 4 days' growth was 34.4%. DOX eliminated P388/S cells from mixed cultures. Nitrogen mustard [(HN2) NCS-762] and x-rays were selectively toxic to P388/R cells. The selectivity of HN2 and x-rays was observed in a narrow dose range by the absence of selective inhibition at low doses, the decreased proportion of P388/R cells at moderate doses, and the killing of all cells in mixed cultures at high doses. Combination treatment of mixed cultures with DOX plus x-rays, or HN2 plus x-rays, produced complete inhibition of growth. Mixed cultures recovered after treatment with DOX plus HN2 contained only P388/R cells. Results obtained by colony-formation assay showed the same patterns of relative sensitivity for P388/R and P388/S cells as the data obtained by flow cytometry (FCM) selectivity assay. FCM analysis of mixed cultures detected selective toxicity for P388/R cells after treatments, characterized by approximately 1 log higher cell killing of P388/R cells than of P388/S cells. It was concluded that FCM analysis of mixed cultures provided a sensitive and reliable assay for fast screening of drugs for selective toxicity to multidrug-resistant cells.
Student noticing in classroom settings: A process underlying influences on prior ways of reasoning

Abstract This study examines the degree to which individual and social aspects of student noticing in classroom settings during new learning influence students’ ways of reasoning about previously-encountered concepts. Seventh- and eighth-grade students (N = 7) participated in an instructional unit on quadratic functions (the new concept) and clinical pre- and post-interviews examined students’ ways of reasoning about linear functions (the previously-encountered concept). Qualitative analysis of the interview and classroom data revealed that (a) five of seven students’ ways of reasoning on linear function tasks were productively influenced from pre- to post-interview, and (b) all seven students came to notice covariation during the quadratic functions instructional unit by way of particular social processes. Furthermore, the changes in ways of reasoning about linear functions were conceptually connected to what students noticed about quadratic functions. This study serves as a proof of concept that the process of noticing during new learning about quadratic functions can be leveraged to productively influence students’ ways of reasoning about linear functions. This study could also serve as a model for how to enhance instruction for other mathematics topics to similarly achieve productive influences on ways of reasoning about previously-encountered concepts.
Observations on the role of light, temperature, age, and sex in the response of screw-worm flies to attractants.

Observations made while screening candidate attractants for the screw-worm fly, Cochliomyia hominivorax (Coquerel), revealed that light was an environmental factor affecting fly response. In unbaited traps about 25 times more flies were captured in light than in darkness. At temperatures ranging from 86°-113° F, 3 times as any flies were captured as at those from 67°-80°. Oviposition took place in temperatures ranging from 86°-113°; the greatest number of egg masses was deposited at 104°±6°. In baited traps very few 1- to 2-day-old flies were captured among 1- to 7-day-old flies tested; the greatest attraction was obtained when the flies were 3-4 days old. Among flies 6–8 days old tested for their attraction to liver and blood. about 5 times more females than males were trapped.
A COMPARISON OF AMALGAMATED AND NON-AMALGAMATED ZINC ELECTRODES

ABSTRACT A comparison of amalgamated and non-amalgamated zinc electrodes was made by measuring the polarization at such electrodes in KOH solutions, by measuring the double-layer capacity of these electrodes, and by the use of cyclic voltammetry. In all cases the amalgamated electrodes had a larger discharge capacity and a lower double-layer capacitance. The latter suggests that OH– ion adsorption plays a much larger role in the anodic oxidation of a non-amalgamated electrode than of an amalgamated electrode. However, both types of electrodes seem to be subject to diffusion control in the measurements reported here. There is no unequivocal evidence to determine whether it is the OH– or zincate ion that is limiting the diffusion process.
Platelet Activation and Clopidogrel Effects on ADP‐Induced Platelet Activation in Cats with or without the A31P Mutation in MYBPC3

Background Clopidogrel is commonly prescribed to cats with perceived increased risk of thromboembolic events, but little information exists regarding its antiplatelet effects. Objective To determine effects of clopidogrel on platelet responsiveness in cats with or without the A31P mutation in the MYBPC3 gene. A secondary aim was to characterize variability in feline platelet responses to clopidogrel. Animals Fourteen healthy cats from a Maine Coon/outbred mixed Domestic cat colony: 8 cats homozygous for A31P mutation in the MYPBC3 gene and 6 wild-type cats without the A31P mutation. Methods Ex vivo study. All cats received clopidogrel (18.75 mg PO q24h) for 14 days. Before and after clopidogrel treatment, adenosine diphosphate (ADP)-induced P-selectin expression was evaluated. ADP- and thrombin-induced platelet aggregation was measured by optical aggregometry (OA). Platelet pVASP and ADP receptor response index (ARRI) were measured by Western blot analysis. Results Platelet activation from cats with the A31P mutation was significantly (P = .0095) increased [35.55% (18.58–48.55) to 58.90% (24.85–69.90)], in response to ADP. Clopidogrel treatment attenuated ADP-induced P-selectin expression and platelet aggregation. ADP- and PGE1-treated platelets had a similar level of pVASP as PGE1-treated platelets after clopidogrel treatment. Clopidogrel administration resulted in significantly lower ARRI [24.13% (12.46–35.50) to 11.30% (−7.383 to 23.27)] (P = .017). Two of 13 cats were nonresponders based on OA and flow cytometry. Conclusion and Clinical Importance Clopidogrel is effective at attenuating platelet activation and aggregation in some cats. Cats with A31P mutation had increased platelet activation relative to the variable response seen in wild-type cats.
Replacing PCR with COLD-PCR enriches variant DNA sequences and redefines the sensitivity of genetic testing in cancer

1796 Introduction: The Polymerase Chain Reaction (PCR) has become the cornerstone of molecular diagnosis, with almost every genetic test aiming to identify DNA sequence variation incorporating PCR. A commonly encountered problem is that variant DNA sequences exist in the presence of a large majority of wild type alleles such as when DNA is obtained from heterogeneous cancer biopsies or when fetal alleles are sought in maternal blood. As a result, downstream assays are severely limited in their ability to identify subtle genetic changes that can have profound impact in clinical decision-making and outcome. We describe Co-amplification at Lower Denaturation temperature (COLD-PCR), a novel form of PCR that amplifies minority alleles selectively from mixtures of wild-type and mutation-containing sequences irrespective of the mutation type or position on the sequence (Nature Medicine, In Press). Methods: In COLD-PCR, an intermediate annealing temperature is used during PCR-cycling to allow cross-hybridization of mutant and wild type alleles; hetero-duplexes, which melt at lower temperatures than homo-duplexes, are then selectively denatured and amplified at Critical Denaturation Temperature (Tc), while homo-duplexes remain double-stranded and do not amplify efficiently. By fixing the denaturation temperature to Tc, mutations at any position along the sequence are enriched during COLD-PCR amplification. To validate COLD-PCR, we used serial dilutions of DNA from tumor-derived cell lines containing point mutations or micro-deletions at different positions along p53 exon 8 and Kras exon 1 (codons 12-13), or samples with micro-deletions in EGFR exon 19. In addition, genomic DNA from a series of colon and lung cancer surgical specimens, and plasma-circulating DNA collected under IRB approval were utilized for validation on clinical specimens. Results: By replacing regular PCR with COLD-PCR prior to application of a range of assays (Sanger sequencing; Pyrosequencing; MALDI-TOF; dHPLC; RFLP; and Taqman) we improved mutation detection sensitivity up to 100-fold and identified several additional p53/Kras/EGFR mutations in heterogeneous cancer samples. 4 of 43 surgical samples and 3 of 10 plasma samples tested contained clinically important mutations that were not detected by any of the methods tested when preceded by regular-PCR, but they were detectable following COLD-PCR. Conclusion: Replacement of regular PCR with COLD-PCR provides a universal boost to most mutation detection technologies and enables them to be used with the required confidence in routine screening of cancer specimens for somatic mutations, including low-level mutation screening of surgical/FFPE tumor samples or bodily fluids. COLD-PCR is also anticipated to find application in pre-natal diagnosis, in infectious diseases and in epigenetics.
Exploring the nap paradox: are mid-day sleep bouts a friend or foe?

The mid-day nap, sometimes called a siesta, is a ubiquitous occurrence across the lifespan. It is well established that in addition to reducing sleepiness, mid-day naps offer a variety of benefits: memory consolidation, preparation for subsequent learning, executive functioning enhancement, and a boost in emotional stability. These benefits are present even if a sufficient amount of sleep is obtained during the night prior. However, we present a paradox: in spite of these reported benefits of naps, frequent napping has also been associated with numerous negative outcomes (eg, cognitive decline, hypertension, diabetes), particularly in older populations. This association exists even when statistically controlling for relevant health- and sleep-affecting determinants. An emerging hypothesis suggests inflammation is a mediator between mid-day naps and poor health outcomes, yet further research is necessary. Given this, it may be premature to ‘prescribe’ naps as a health enhancer. Herein, we aggregate findings from several branches of sleep research (eg, developmental neuroscience, cognitive neuroscience, sleep medicine) to critically examine the paradoxical role of naps in cognitive and somatic health. This review uncovers gaps in the literature to guide research opportunities in the field.
Long-Term Impact of Childhood Abuse and Neglect on Crime and Violence

This article begins with a description of the current state of knowledge on the “cycle of violence,” broadly defined. Subsequent sections focus on the impact of childhood neglect on criminal consequences, potential gender differences in criminal consequences, the extent to which sexual abuse leads to sexual offending, and the extent to which child abuse and neglect lead to intimate partner violence and the intergenerational transmission of abuse and neglect. There is a brief discussion of protective factors, and the article concludes with recommendations for future research and implications for practice.
Deep Sparse-coded Network (DSN)

We present Deep Sparse-coded Network (DSN), a deep architecture based on multilayer sparse coding. It has been considered difficult to learn a useful feature hierarchy by stacking sparse coding layers in a straightforward manner. The primary reason is the modeling assumption for sparse coding that takes in a dense input and yields a sparse output vector. Applying a sparse coding layer on the output of another tends to violate the modeling assumption. We overcome this shortcoming by interlacing nonlinear pooling units. Average- or max-pooled sparse codes are aggregated to form dense input vectors for the next sparse coding layer. Pooling achieves nonlinear activation analogous to neural networks while not introducing diminished gradient flows during the training. We introduce a novel backpropagation algorithm to finetune the proposed DSN beyond the pretraining via greedy layerwise sparse coding and dictionary learning. We build an experimental 4-layer DSN with the l 1 -regularized LARS and the greedy-l 0 OMP, and demonstrate superior performance over a similarly-configured stacked autoencoder (SAE) on CIFAR-10.
The servant class city: urban revitalization versus the working Poor in San Diego

The goal of David Karjanen’s Servant Class City is to link two arenas of scholarship that, despite treating closely related subjects, infrequently inform one another: the study of urban redevelopme...
Experimental Approaches for the Detection of Chromosomal Malsegregation Occurring in the Germline of Mammals

Existing and newly proposed methods to detect the induction of heritable aneuploidy are summarized, and their favorable and unfavorable features discussed. Among the tests involving direct chromosomal examination, those involving study of pronuclear chromosomes at first cleavage are judged to be the most universally informative and reliable, provided tertiary trisomy can be ruled out. Measurement of postmidterm (fetal) death is proposed as a trisomy prescreen that can be readily combined with a dominant-lethal test. Among the genetic procedures for identifying the results of malsegregation events, direct detection of aneuploids has a number of advantages over complementation methods, in which only a fraction of the products of aneuploid gametes is detectable. Direct detection of aneuploids must, however, be restricted to sex chromosomes if postnatal animals are examined. A genetic marker system to detect autosomal trisomies in fetuses is proposed. An examination of experimental parameters that might maximize induction of malsegregation leads to the recommendation to include preleptotene among exposed germ-cell stages.
Contact activation by the intrinsic pathway of blood plasma coagulation

Abstract It is well known that the biomaterial surfaces that comprise biomedical devices will initiate blood coagulation. This can occur through the adhesion and activation of platelets, but also through the activation of the proteins of the intrinsic coagulation cascade. Nominally, this involves activation of the zymogen FXII (Hageman Factor) which in turn activates FXI, prekallikrein and high-molecular-weight kininogen to form an activation complex. The end result of this sequence of zymogen/enzyme conversion steps is the production of thrombin, the conversion of fibrinogen to fibrin and the development of fibrin strands. In this chapter, we discuss the proteins of the intrinsic pathway, the traditional view of contact activation, and finally alternative ideas about the activation of this important pathway. Notably, we attempt to reconcile the inconsistencies between protein adsorption and function at biomaterial surfaces and the traditional views of contact activation.
Effects of initial conditions on the coalescence of micro-bubbles:

The effects of initial conditions on the coalescence of two equal-sized air micro-bubbles (R0) in water are studied using the lattice Boltzmann method. The focus is on effects of two initial set-up...
Psychopathic personality traits as a form of dispositional capability for suicide.

Abstract The capability to enact lethal self-harm has recently been highlighted as a critical risk factor for suicidal behavior. Klonsky and May's (2015) three step theory of suicide (3ST) expanded upon the construct of the capability for suicide by dividing it into categories: dispositional, acquired, and practical. The current study examined constructs of Patrick and colleagues’ (2009) triarchic model of psychopathy as indicators of dispositional capability in gun owners, a sample at heightened risk for death by suicide (Anestis and Houtsma, 2017). We anticipated that specific psychopathic traits would exhibit robust associations with other components of the capability for suicide. In a sample of 300 gun-owning adults, Boldness was uniquely related to all indicators of practical capability in both male and female gun owners, and a Boldness*Meanness interaction predicted the highest levels of some capability components. These results are consistent with theoretical conceptualizations of the triarchic model. Our findings indicate that, among US gun owners, dispositional factors may impact comfort with and aptitude with guns, which may enhance our understanding of which gun owners are at the greatest risk of gun suicide should they develop suicidal thoughts.
Atherogenic and anti-atherogenic factors in the human diet

New atherosclerosis causative factors and preventive modalities have been identified. Atherogenic factors include lipid oxidation products, such as cholesterol oxidation products, malonaldehyde and other aldehydes; trans-fatty acids; some saturated fatty acids (lauric, myristic and possibly palmitic acids); and myristic acid plus cholesterol. Lipid oxidation products are well suited to induce arterial damage, based on their known cytotoxic effects; evidence also indicates the possibility of plaque promotion and stimulation of thrombogenesis. Anti-atherogenic factors include antioxidants, fish oils and other polyunsaturates (if protected from oxidation), fibre and trace minerals such as copper, manganese, selenium and zinc. Iron is unique, being considered as both a potential promoter of atherosclerosis (component of ferritin, conceivably inducing lipid oxidation) and a possible anti-atherogenic component (of antioxidant enzyme catalase). It is apparent that an entire new series of research challenges has been uncovered.