cssi/SciSciGPT-SciSciNet huggingface dataset:
Differential time dependency of antiproliferative and apoptotic effects of taxol in human prostate tumors.

Abstract The pharmacodynamics of taxol in human prostate tumors were studied using histocultures of radical prostatectomy specimens from 34 patients. The results showed that taxol inhibited DNA synthesis and induced apoptosis in all tumors. The taxol-induced DNA inhibition and the apoptotic index increased with drug concentration, but reached a maximal plateau level at a concentration between 120 and 1,200 nM. Increasing the concentration by 10- to 100-fold to 12,000 nM did not significantly increase either effect. To address the existing controversy regarding the effect of treatment duration on cytotoxicity, we evaluated two treatment schedules, (i.e., 24 and 96 hours). Prolonging the treatment time from 24 to 96 hours significantly increased the average maximal inhibition of DNA synthesis (Emax) from 47% to 70% (p 300,000- and a 14,000-fold range for the 24 and 96 hour treatments, respectively. In conclusion, data of the present study demonstrate (1) antiproliferative and apoptotic effects of taxol in human prostate tumors, (2) that neither effect was significantly enhanced by increasing the drug concentration above 1,200 nM, and (3) that the antiproliferative effect was affected more significantly by drug exposure time than the apoptotic effect.
COMMENTS ON EGER'S “A TALE OF TWO CONTROVERSIES”

. This commentary on Martin Eger's “A Tale of Two Controversies” focuses on three criticisms: first, the shifting status of the claims of creationism in the article; second, new developments in moral philosophy which run counter to Eger's discussion; and third, the inadequate treatment of pedagogical and curricular principles.
Predictive factors for pancreatic fistula following pancreatectomy

Postoperative pancreatic fistula is a significant contributor to morbidity following proximal and distal pancreatic resections. In recent decades, the incidence of fistula has ranged from 2 to 33 %; however, the consistent identification of risk factors has been difficult due to significant variability in the definition of pancreatic fistula. The purpose of this study was to use the highest level evidence available in the literature to present risk factors thus far identified as significant predictors of fistula occurrence. Another endpoint will address those risk factors which have been shown to have a clinical impact on the patient. This review will conclude by discussing comprehensive risk models that interpret the aggregate fistula risk for a patient based on the presence of weighted risk factors. The contemporary surgical literature suggests many risk factors for fistula development, which can be categorized as either endogenous, operative, or perioperative. The advent of the International Study Group of Pancreatic Fistula (ISGPF) scheme created universal definitions for fistula that delineate between biochemical and clinically relevant fistulas. This classification system has allowed for the elucidation of risk factors for clinically impactful fistula and enabled the development of risk scores for predicting fistula occurrence after major pancreatic resections, which are useful in clinical management and comparative research.
Human renal organic anion transporters: Characteristics and contributions to drug and drug metabolite excretion

The kidney is a key organ for promoting the excretion of drugs and drug metabolites. One of the mechanisms by which the kidney promotes excretion is via active secretion. Secretion of drugs and their metabolites from blood to luminal fluid in the nephron is a protein-mediated process that normally involves either the direct or indirect expenditure of energy. Renal transporters for organic anions are located in the proximal tubule segment of the nephron. The primary transporters of organic anions on the basolateral membrane (BLM) of proximal tubule cells are members of the organic anion transporter (OAT) family (mainly OAT1 and OAT3). The sulfate-anion antiporter 1 (SAT-1; hsat-1) may also contribute to organic anion transport at the basolateral membrane. On the apical membrane, the multi-drug resistance-associated protein 2 (MRP2) is an important transport protein to complete the secretion process. However, there are several transport proteins on the basolateral and apical membranes of proximal tubule cells in human kidneys that have not been fully characterized and whose role in the secretion of organic anions remains to be determined. This review will primarily focus on the human renal basolateral and apical membrane transporters for organic anions that may play a role in the excretion of drugs and drug metabolites.
Elastohydrodynamic film thickness measurements of artificially produced nonsmooth surfaces

Optical interferometry is used to measure the elastohydrodynamic (EHD) film thickness associated with artificially produced nonsmooth surfaces. The nonsmooth surfaces are produced by modifying the surfaces of highly-polished balls with irregularities in the form of multiple grooves and dents. By closely spacing these irregularities it is possible not only to produce depressions on the surface of the balls but also to generate pseudo asperities. The average roughness wavelength of this artificially-produced, nonsmooth, surface approximates the average fundamental roughness wavelength found on surfaces of some mechanical elements operating under concentrated contact. By comparing the measured film thickness profiles to the stylus traces of the irregularities, it was possible to observe the local deformations associated with micro-EHD pressure generation. In both pure rolling and pure sliding conditions the artificially-produced asperities are deformed and complete separation exists between them and the mating surface. Such findings demonstrate the importance of local surface topography and resulting micro-EHD effects on the film thickness between rough surfaces in concentrated contact. Sliding data are presented which demonstrate a severe constriction, caused by the irregularities, at the exit of the Hertzian region.
Stress, learning style, resilience factors, and ways of coping in Alzheimer family caregivers:

Family caregiving is increasing steadily as our overall population ages. Most research has studied caregivers in relation to stress level, anxiety, and depression. This study investigated the relat...
Nipping fear in the bud: inhibitory control in the amygdala.

Cortical and thalamic inputs to the lateral amygdala are recruited during auditory fear conditioning. In this issue of Neuron , Pan et al. describe a new mechanism of GABA-mediated modulation at these synapses, involving target-specific suppression of glutamate release through differential activation of GABAb receptors on glutamatergic inputs to neurons and interneurons.
Delaying Transmissions in Data Communication Networks to Improve Transport-Layer Performance

Packet losses in the network have a considerable performance impact on transport-layer throughput. For reliable data transfer, lost packets require retransmissions and thus cause very long delays. This tail of the packet delay distribution causes performance problems. There are several approaches to trading off networking resources up-front to reduce long delays for some packets (e.g., forward error correction, network coding). We propose packet pacing as an alternative that changes traffic characteristics favorably by adding intentional delay in packet transmissions. This intentional delay counters the principle of best effort but can reduce the burstiness of traffic and improve overall network operation - in particular in network with small packet buffers. As a result, pacing improves transport-layer performance, providing a tradeoff example where small amounts of additional delay can significantly increase connection bandwidth. We present a Queue Length Based Pacing (QLBP) algorithm that paces network traffic using a single queue and that can be implemented with small computational and memory overhead. We present a detailed analysis on delay bounds and the quantitative impact of QLBP pacing on network traffic. Through simulation, we show how the proposed pacing technique can improve connection throughput in small-buffer networks.
Analysis of scattering loss and effective index step in asymmetric cladding surface etched distributed bragg reflector lasers

The relationship between the physical fabrication of asymmetric cladding surface etched DBR structures and the resulting optical characteristics are characterized. The effective index step and DBR scattering loss for these structures is determined.
Constraint management in fuel cells: a fast reference governor approach

The air supply system in a fuel cell may be susceptible to saturation during transient driving conditions. The air compressor surge and choke can disrupt the flow of air into the cathode and negatively impact fuel cell power generation. Low partial oxygen pressure in the cathode can damage the stack and reduce its life. A load governor, added to the air supply control system, can monitor the transients and prevent constraint violation by modifying the reference current command to the fuel cell stack. In this paper, we develop such a load governor using two approaches. The first approach is based on on-line model predictive control and the second approach utilizes a fast reference governor. We discuss the performance and computational requirements of each method. We propose a modification to the fast reference governor design to make it applicable to a nonlinear plant.
Comparison of floating gate neural network memory cells in standard VLSI CMOS technology

Several floating gate MOSFET structures, for potential use as analog memory elements in neural networks, have been fabricated in a standard 2 mu m double-polysilicon CMOS process. Their physical and programming characteristics are compared with each other and with similar structures reported in the literature. None of the circuits under consideration require special fabrication techniques. The criteria used to determine the structure most suitable for neural network memory applications include the symmetry of charging and discharging characteristics, programming voltage magnitudes, the area required, and the effectiveness of geometric field enhancement techniques. This work provides a layout for an analog neural network memory based on previously unexplored criteria and results. The authors have found that the best designs (a) use the poly1 to poly2 oxide for injection; (b) need not utilize 'field enhancement' techniques; (c) use poly1 to diffusion oxide for a coupling capacitor; and (d) size capacitor ratios to provide a wide range of possible programming voltages. >
Visually mining Web user clickpaths

As powerful as clickpath mining methods can be, they often lead to huge incomprehensible and non-interesting result sets. Our clickpath mining practice at MSN was faced with challenges of keeping analysts closer to the data exploration process, revealing powerful insight from clickpath mining that business owners can directly act upon. These challenges stressed the importance of an interactive and visual representation of clickpath mining results. Most products today that can perform clickpath visualization do so by presenting massive cross-weaving web graphs. We present a new type of clickpath visualization which focuses only on clickpaths of interest, simplifying the visualization space while still retaining the same degree of mineable knowledge in the data. We also describe visualization techniques we have used to enhance the detection of interesting clickpath patterns from data, and provide a real-life case study that has benefited from the use of our implemented clickpath visualizer PAVE.
Effects of School-Wide Positive Behavioral Interventions and Supports on Child Behavior Problems

OBJECTIVE: School-Wide Positive Behavioral Interventions and Supports (SWPBIS) is a universal prevention strategy currently implemented in >16 000 schools across the United States. SWPBIS intends to reduce students’ behavior problems by altering staff behaviors and developing systems and supports to meet children’s behavioral needs. The current study reports intervention effects on child behaviors and adjustment from an effectiveness trial of SWPBIS. METHODS: The sample of 12 344 elementary school children was 52.9% male, 45.1% African American, and 46.1% Caucasian. Approximately 49% received free or reduced-priced meals, and 12.9% received special education services at baseline. The trial used a group randomized controlled effectiveness design implemented in 37 elementary schools. Multilevel analyses were conducted on teachers’ ratings of children’s behavior problems, concentration problems, social-emotional functioning, prosocial behavior, office discipline referrals, and suspensions at 5 time points over the course of 4 school years. RESULTS: The multilevel results indicated significant effects of SWPBIS on children’s behavior problems, concentration problems, social-emotional functioning, and prosocial behavior. Children in SWPBIS schools also were 33% less likely to receive an office discipline referral than those in the comparison schools. The effects tended to be strongest among children who were first exposed to SWPBIS in kindergarten. CONCLUSIONS: These findings provide support for the hypothesized reduction in behavior problems and improvements in prosocial behavior and effective emotion regulation after training in SWPBIS. The SWPBIS framework appears to be a promising approach for reducing problems and promoting adjustment among elementary school children.
Manuscript Bleed-through Removal via Hysteresis Thresholding

Many types of degradation can render ancient manuscripts very hard to read. In bleed-through, the text from the reverse, or verso, side of a page seeps through into the front, or recto. In this paper, we propose hysteresis thresholding to greatly reduce bleed-through. Thresholding alone cannot properly separate ink and bleed-through because the ranges of intensities for the two classes overlap. Hysteresis thresholding overcomes this limitation via the two steps of thresholding and ink regrowth. In order to provide quantitative measures of the effectiveness of this approach, we constructed a novel dataset which features bleed-through and has available ground truth. We evaluated our method and a number of previously proposed approaches on ink pixel precision and recall. Hysteresis thresholding significantly improves over existing methods.
Generalized “Satisfaction of Search”: Adverse Influences on Dual-Target Search Accuracy

The successful detection of a target in a radiological search can reduce the detectability of a second target, a phenomenon termed satisfaction of search (SOS). Given the potential consequences, here we investigate the generality of SOS with the goal of simultaneously informing radiology, cognitive psychology, and nonmedical searches such as airport luggage screening. Ten experiments utilizing nonmedical searches and untrained searchers suggest that SOS is affected by a diverse array of factors, including (1) the relative frequency of different target types, (2) external pressures (reward and time), and (3) expectations about the number of targets present. Collectively, these experiments indicate that SOS arises when searchers have a biased expectation about the low likelihood of specific targets or events, and when they are under pressure to perform efficiently. This first demonstration of SOS outside of radiology implicates a general heuristic applicable to many kinds of searches. In an example like airport luggage screening, the current data suggest that the detection of an easy-to-spot target (e.g., a water bottle) might reduce detection of a hard-to-spot target (e.g., a box cutter).
Increased Hypothalamic Protein Tyrosine Phosphatase 1B Contributes to Leptin Resistance with Age

Animals at advanced ages exhibit a reduction in central leptin sensitivity. However, changes in growth, metabolism, and obesity risk occur much earlier in life, particularly during the transition from youth to middle age. To determine when initial decreases in central leptin sensitivity occur, leptin-dependent suppression of food intake was tested in 8-, 12-, and 20-wk-old male, chow-fed Sprague Dawley rats. Intracerebroventricular leptin injection (3 μg) suppressed 24-h food intake in 8- and 12-wk-old rats (P < 0.05) but not 20-wk-old rats. To identify potential cellular mediators of this resistance, we focused on protein tyrosine phosphatase 1B (PTP1B), a recently described inhibitor of leptin signaling. PTP1B protein levels, as determined by Western blot, were significantly higher in mediobasal hypothalamic punches collected from 20-wk-old rats, compared with 8-wk-old rats (P < 0.05). When 20-wk-old rats were fasted for 24 h, levels of hypothalamic PTP1B decreased (P < 0.05), coincident with a restoration of leptin sensitivity. To directly test whether inhibition of PTP1B restores leptin sensitivity, 20-wk-old chow-fed rats were pretreated with a pharmacological PTP1B inhibitor 1 h before leptin, and 24-h food intake was recorded. As expected, leptin alone produced a small but nonsignificant reduction in food intake. However, pretreatment with the PTP1B inhibitor resulted in a marked improvement in leptin-dependent suppression of food intake (P < 0.05). These data are consistent with the hypothesis that increases in PTP1B contribute to hypothalamic leptin resistance as rats transition into middle age.
Simplification of DES models of M/M/1 tandem queues by approximating WIP-dependent inter-departure times

This paper presents two algorithms to analytically approximate work in process (WIP)-dependent inter-departure times for tandem queues composed of a series of M/M/1 systems. The first algorithm is used for homogeneous tandem queues, the second for such with bottlenecks. Both algorithms are based on the possible combinations of distributing the WIP on the queues. For each combination the time to the next departure is estimated. A weighted average of all estimated times of each WIP level is calculated to get the expected mean inter-departure time. The generated inter-departure times are used in a simple model of the tandem queue. The inter-departure times, the average WIP and average cycle time of the tandem queue and the simple model are compared in several tandem queue parameterizations. Results show only a small error between the simple model and the tandem queue, rendering this approach applicable in many applications.
Acute Myeloid Leukemia With t(6;9)(p23;q34) Is Associated With Dysplasia and a High Frequency of flt3 Gene Mutations

We report 12 cases of t(6;9)(p23;q34)-positive acute myeloid leukemia (AML), all classified using the criteria of the World Health Organization classification. There were 10 women and 2 men with a median age of 51 years (range, 20-76 years). Dysplasia was present in all cases (9 previously untreated), and basophilia was present in 6 (50%). Immunophenotypic studies showed that the blasts were positive for CD9, CD13, CD33, CD38, CD117, and HLA-DR in all cases assessed. CD34 was positive in 11 (92%) of 12, and terminal deoxynucleotidyl transferase was positive in 7 (64%) of 11 cases. The t(6;9) was the only cytogenetic abnormality detected in 7 cases (58%), and 5 cases had additional chromosomal abnormalities. Of 8 cases assessed, 7 (88%) had flt3 gene mutations. We conclude that t(6;9)-positive AML cases have distinctive morphologic features, an immunophenotype suggesting origin from an early hematopoietic progenitor cell, and a high frequency of flt3 gene mutations.
Causal Transient Simulation of Passive Networks with Fast Convolution

A methodology for performing causal transient simulation of passive networks has been described in R. Mandrekar and M. Swaminathan (2005). The methodology is based on signal flow graphs and requires multiple convolutions to be performed at each time step. Since convolution is a computationally expensive operation, it limits the efficiency of the simulation methodology when simulating large sized networks. This paper describes the use of a fast convolution algorithm that improves the simulation efficiency for large sized problems. The paper demonstrates this by simulating a 130-port S-parameter network using signal flow graphs
RELATIONSHIP OF TOLERANCE OF AMBIGUITY AND PLAYFULNESS TO CREATIVITY

The purpose of this study was to investigate the relationship of tolerance of ambiguity and playfulness to creativity. The constructs were measured by the AT-20, the Adult Behavior Inventory of Playfulness, and the Myers-Briggs Type Indicator Creativity Index. Tolerance of ambiguity and playfulness were significantly correlated .31 and .48 with creativity. The correlation of playfulness and creativity remained significant when tolerance for ambiguity was controlled. The discussion includes the role of tolerance for ambiguity in understanding playfulness and creativity, creativity as a multidimensional construct, and the use of the Myers-Briggs Creativity Index as a measure of creative style.
Lateral displacement of the mandible in Rhesus monkeys

Summary Lateral displacement of the mandible was induced experimentally in five adult male Rhesus monkeys. Following from 2½2 weeks to 19 months, the animals were sacrificed and examined histologically. Two of the monkeys received H3 proline 4 months prior to sacrifice and radioautographs were prepared. The lateral displacement apparently caused great discomfort because the monkeys refused to eat and lost weight rapidly for a few months. After about 12 months, the monkeys could again eat their normal diet to the extent they started to gain weight slowly. The histological and radio-autographic findings indicated almost no changes of the articular surfaces of the temporomandibular joints. However, extensive reorganization of the neck of the condyles was observed. Severe periodontal trauma and extensive movements of the teeth occurred in spite of the fact that the teeth in each jaw were splinted firmly together.
Regulation of intestinal apolipoprotein A‐IV synthesis

Apolipoprotein (apo) A-IV is a protein synthesized, in humans, only by the small intestine. It has a molecular weight of 46 000 Da. This paper summarizes the evidence supporting its role as a satiety factor following the ingestion of fat. This function of apo A-IV is unique and not shared by other apolipoproteins, including apo A-I. The satiety effect of apo A-IV is centrally mediated. The mechanism of how apo A-IV inhibits food intake is not clear but it probably acts by inhibiting both gastric acid secretion as well as gastric motility. Lipid absorption stimulates apo A-IV synthesis and secretion by the jejunum. In addition to lipid feeding, there is evidence that a factor which is released as a result of lipid absorption in the distal small intestine also stimulates the synthesis and release of apo A-IV by the jejunum. This factor is probably PYY.
Bafilomycin-sensitive acid secretion by mantle epithelium of the freshwater clam, Unio complanatus

This study reports the effects of a series of putative inhibitors of proton translocation on electrogenic acid secretion by the isolated shell-facing mantle epithelium of the freshwater clam, Unio complanatus. In this epithelium, adenosine 3',5'-cyclic monophosphate (cAMP)-dependent acid secretion is electrogenic and equivalent to the cAMP-dependent short-circuit current (Isc) when mounted in a Ussing-type flux chamber. Bafilomycin A1, a specific inhibitor of vacuolar-type H(+)-ATPases (V-type ATPases), inhibited cAMP-dependent electrogenic acid secretion, with an IC50 of 7 nM and a maximum effect at 100 nM. Inhibition of acid secretion by bafilomycin A1 occurred only when added to the shell side and was not reversed by repeated washings. Concomitant with the inhibition of cAMP-dependent Isc by bafilomycin A1, the electrical potential difference across the shell-facing membrane depolarized, and the conductance ratio of the apical to basolateral membranes decreased. The cAMP-dependent Isc and cAMP-dependent acid secretion also were inhibited by dicyclohexyl-carbodiimide, diethylstilbestrol, N-ethylmaleimide, and tributyltin. Amiloride, omeprazole, oligomycin, venturicidin, and ouabain had no effect on either cAMP-dependent Isc or cAMP-dependent acid secretion. The cAMP-dependent Isc and cAMP-dependent acid secretion were not affected by Na(+)-free or K(+)-free solutions. Finally, the cAMP-dependent Isc was strongly dependent on the pH of the shell-facing compartment, with 50% inhibition of the maximum cAMP-dependent Isc occurring at pH 6.0 and complete inhibition at pH 5.5.(ABSTRACT TRUNCATED AT 250 WORDS)
COMPLETENESS THEOREM FOR A PRODUCT OF SELF-ADJOINT MATRICES

It is proven that the matrices AB and BA formed from the product a positive definite self-adjoint matrix A and a self-adjoint matrix B has real eigenvalues and a complete set of eigenvectors. If B is positive (negative) semidefinite the eigenvalues are greater (less) than or equal to zero. These properties have been useful in the analysis of multicomponent diffusion and distillation processes.
Techniques for estimation of design diversity for combinational logic circuits

Design diversity has long been used to protect redundant systems against common-mode failures. The conventional notion of diversity relies on "independent" generation of "different" implementations of the same logic function. This concept is qualitative and does not provide a basis to compare the reliabilities of two diverse systems. In a recent paper, we presented a metric to quantify diversity among several designs. The problem of calculating the diversity metric is NP-complete and can be of exponential complexity. In this paper we present techniques to estimate the value of the design diversity metric. For datapath designs, we have formulated very fast techniques to calculate the value of the metric by exploiting the regularity in the datapath structures. For general combinational logic circuits, we present an adaptive Monte-Carlo simulation technique for estimating bounds on the value of the metric. The adaptive Monte-Carlo simulation technique provides accurate estimates of the design diversity metric; the number of simulations used to reach this estimate is polynomial (instead of exponential) in the number of circuit inputs. Moreover, the number of simulations can be tuned depending on the desired accuracy.
Dividend Policy and Agency Effects: A Look at Financial Firms

This paper attempts to determine the relationship between the dividend policy of financial firms and a number of ownership and board control variables as well as two governance provisions—cumulative voting and staggered boards. Agency theory contends that dividends can be used as a substitute control device when ownership, board or governance provisions are unfavorable for shareholders. The evidence indicates that firms with lower CEO, institutional and hedge fund ownership pay higher dividends. Also, cumulative voting has a greater impact on dividend policy than staggered boards. These results suggest that firms adjust their dividend policy in response to control changes caused by ownership structure and governance provisions.
Enhanced Procedures for Direct Trajectory Optimization Using Nonlinear Programming and Implicit Integration

Trajectory optimization is key to the design and analysis of aerospace vehicles. The use of implicit integration combined with modern nonlinear programming packages has proven to be an effective technique for trajectory optimization. To provide greater fidelity and robustness, enhanced procedures have been developed. General procedures are presented for implicit integration schemes of arbitrary order, automatic variable scaling and grid refinement. The implicit integration methods of interest are collocation, quadrature and pseudo-spectral integration. Computation experiences applying and comparing these methods to interplanetary spacecraft and aircraft problems are given. These procedures have demonstrated substantial improvements in integration accuracy and robust operations.
Acinetobacter baumannii bloodstream infection while receiving tigecycline: a cautionary report

Objectives: Tigecycline has shown in vitro activity against Acinetobacter baumannii. Yet, published clinical experience with tigecycline use outside clinical trials is lacking. We describe, for the first time, bloodstream infection caused by tigecycline-non-susceptible A. baumannii occurring in patients receiving tigecycline for other indications. The possible mechanisms of resistance and pharmacokinetic limitations of the drug are addressed. Methods: The clinical records of involved patients were systematically reviewed. Tigecycline susceptibility testing was initially performed using the Etest method and confirmed by agar dilution. Involved isolates underwent PFGE and exposure to phenyl-arginine-b-naphthylamide (PAbN), an efflux pump inhibitor. Results: Two patients developed A. baumannii bloodstream infection while receiving tigecycline. Tigecycline was administered for other indications for 9 and 16 days, respectively, before the onset of A. baumannii infection. Patient 1 died of overwhelming A. baumannii infection and Patient 2 recovered after a change in antibiotic therapy. The MICs of tigecycline were 4 and 16 mg/L, respectively. Both isolates had a multidrug-resistant phenotype and were genotypically unrelated. After exposure to PAbN, the MICs reduced to 1 and 4 mg/L, respectively. Conclusions: To our knowledge, this is the first clinical description of bloodstream infection caused by tigecycline-non-susceptible A. baumannii. Such resistance appears to be at least partly attributable to an efflux pump mechanism. Given the reported low serum tigecycline levels, we urge caution when using this drug for treatment of A. baumannii bloodstream infection.
Intravascular fibrin molecular imaging improves the detection of unhealed stents assessed by optical coherence tomography in vivo

AIMS Fibrin deposition and absent endothelium characterize unhealed stents that are at heightened risk of stent thrombosis. Optical coherence tomography (OCT) is increasingly used for assessing stent tissue coverage as a measure of healed stents, but cannot precisely identify whether overlying tissue represents physiological neointima. Here we assessed and compared fibrin deposition and persistence on bare metal stent (BMS) and drug-eluting stent (DES) using near-infrared fluorescence (NIRF) molecular imaging in vivo, in combination with simultaneous OCT stent coverage. METHODS AND RESULTS Rabbits underwent implantation of one BMS and one DES without overlap in the infrarenal aorta (N = 20 3.5 × 12 mm). At Days 7 and/or 28, intravascular NIRF-OCT was performed following the injection of fibrin-targeted NIRF molecular imaging agent FTP11-CyAm7. Intravascular NIRF-OCT enabled high-resolution imaging of fibrin overlying stent struts in vivo, as validated by histopathology. Compared with BMS, DES showed greater fibrin deposition and fibrin persistence at Days 7 and 28 (P < 0.01 vs. BMS). Notably, for edge stent struts identified as covered by OCT on Day 7, 92.8 ± 9.5% of DES and 55.8 ± 23.6% of BMS struts were NIRF fibrin positive (P < 0.001). At Day 28, 18.6 ± 10.6% (DES) and 5.1 ± 8.7% (BMS) of OCT-covered struts remained fibrin positive (P < 0.001). CONCLUSION Intravascular NIRF fibrin molecular imaging improves the detection of unhealed stents, using clinically translatable technology that complements OCT. A sizeable percentage of struts deemed covered by OCT are actually covered by fibrin, particularly in DES, and therefore such stents might remain prothrombotic. These findings have implications for the specificity of standalone clinical OCT assessments of stent healing.
Rapid Thermal Annealing of Fib-Implanted Ga Shallow Impurity Profiles

In this paper, we present the results of a study to fabricate shallow p+ n junction using Ga FIB implantation in conjunction with rapid thermal annealing (RTA). A focused 75 KeV ion beam with BO mA/cm2 current density and 0.5 μm beam diameter was used to implant Ga into (100) Si substrates at the doses from 1E13 to 5E15/cm2. The annealing temperature is from 600 °C to 1000 °C for various times, 10–30 sec. Secondary ion mass spectrometry (SIMS) and spreading resistance profiling (SRP) were used to measure the implanted Ga atomic and carrier concentration depth profiles. As compared to the conventional broad beam (BB) implantation, the FIB implanted impurity concentration depth profile has a longer tail and thus a deeper p+n junction. The damage generated by the high dose rate implantation is possibly responsible for this phenomenon. The results of SRP measurements of the FIB as-implanted samples show no Scif-anneal ing occured during implantations. p+n diodes fabricated using FIB exhibit good junction properties: ideality factor of 1.1, reverse–bias leakage current of below 5 nA/cm2 at -IV, and breakdown voltage of about 35 V.
Deposition and expression of aerosolized rAAV vectors in the lungs of Rhesus macaques.

The goals of these experiments were to efficiently deliver aerosolized adeno-associated virus (AAV) vector to the lungs of Rhesus macaques and to measure gene transfer and expression. To determine optimal lung deposition, we compared four techniques of delivering aerosolized saline admixed with the radioisotope (99m)technetium ((99m)Tc) nebulized through a mouthpiece (Neb Oral), a laryngeal airway mask (Neb LMA), or an endotracheal tube (Neb ETT), or bronchoscopically delivered by Microsprayer (PennCentury). Total lung deposition fraction, as indicated by gamma scintigraphy, averaged 0.5% (Neb Oral), 1.2% (Neb LMA), 1.8+/-0.4% (Neb ETT), and 62.3+/-11.3% (Microsprayer). Because microspraying was the most efficient method of delivery, we used it to administer saline with (99m)Tc-labeled diethylene-triamine penta-acetic acid (DTPA) admixed with 9 x 10(11) infectious units (i.u.) of AAV serotype 2 (rAAV2) vector encoding green fluorescent protein (GFP; rAAV2-GFP). Initial total and regional lung depositions were quantified by scintigraphy. We analyzed the tissue three weeks later for vector-specific DNA transduction and RNA expression. Radioisotope was detected in all lung regions, reflecting an average dose of 1.33 x 10(10)+/-9.5 x 10(9) i.u. per region. Regional data indicated an increase in expression when the dose exceeded 3 x 10(9) i.u. (P=0.030). We conclude that expression of rAAV2-GFP in lungs appears to be related to depositing a regional threshold dose greater than 3 x 10(9) i.u., easily achieved by bronchoscopic microspraying.
Impact of persistent and adolescent-limited antisocial behaviour on adult health outcomes

Background Persistent engagement in antisocial behaviour across developmental periods is thought to increase the risk for early disease morbidity. However, less is known about potential adverse health outcomes among the much larger subset of individuals with antisocial behaviour limited to adolescence. Methods Using data from the Providence, Rhode Island cohort of the Collaborative Perinatal Project, we examined the association between developmentally based subtypes of antisocial behaviour and health outcomes (n=801). Official arrest records and self-reports of engagement in antisocial behaviour were used to classify participants into antisocial groups (persistent into adulthood, adolescent-limited, no significant problems) that were contrasted across important adult health indicators. Results With few exceptions, those with persistent antisocial behaviour had the highest prevalence of each health problem. Compared to those with no antisocial behaviour, participants with persistent problems had poorer overall health and significantly elevated odds of cardiovascular problems, wheezing, lower back pain, cancer, serious injury and emergency department visits. Those with adolescent-limited behaviour experienced significantly increased odds of health concerns including poorer overall health, hypercholesterolaemia, acute respiratory problems and wheezing, lower back pain and emergency department visits compared to participants with no antisocial behaviour. Both antisocial groups reported barriers to healthcare access. Conclusions Findings highlight the impact of persistent antisocial behaviour on adult health, and suggest that antisocial behaviour limited to adolescence is also an important marker of poor health. Given that antisocial behaviour during adolescence is an important early marker of adverse health outcomes, youth exhibiting serious behavioural problems should be targeted for preventive interventions.
Retroviral gene transfer induced constitutive expression of interleukin-2 or interferon-gamma in irradiated human melanoma cells.

Cytokines are important modulators of host antitumor responses. Two of these cytokines, interleukin-2 (IL-2) and interferon gamma (IFN-gamma), are produced after antigen-induced activation of helper lymphocytes. The cytokines are released into the immediate vicinity where they either interact with the appropriate receptors on effector cell populations or are rapidly degraded. To mimic this physiologic release of cytokines at the effector-target site, we used retroviral vectors to transduce melanoma cells with the IL-2 or IFN-gamma cDNA. Five melanoma cell lines were transduced with IL-2- or IFN-gamma-containing vectors and secreted IL-2 at 1 to 40 U/mL/10(6) cells/24 h or IFN-gamma 1 to 8 U/mL/10(6) cells/24 h, respectively. After gamma irradiation, these cells continued to secrete cytokines for about 3 to 4 weeks. Secretion of IFN-gamma induced upregulation of major histocompatibility complex class I molecules in a subset of melanoma cell lines. IL-2 production by human melanoma xenografts induced tumor rejection in BALB/c nu/nu mice, showing the in vivo effect of this cytokine. This study shows that (1) human melanoma cells can be stably transduced with cytokine- containing retroviral vectors; (2) cytokines are secreted constitutively by the transduced tumor cells and have the expected biologic effects in vitro and in vivo; and (3) after gamma irradiation, cytokines continue to be secreted for several weeks. These data suggest that irradiated cytokine-secreting allogenic or autologous tumor cells can be used in vaccination protocols for cancer patients.
Differential Expression and Function of PDE8 and PDE4 in Effector T cells: Implications for PDE8 as a Drug Target in Inflammation.

Abolishing the inhibitory signal of intracellular cAMP is a prerequisite for effector T (Teff) cell function. The regulation of cAMP within leukocytes critically depends on its degradation by cyclic nucleotide phosphodiesterases (PDEs). We have previously shown that PDE8A, a PDE isoform with 40-100-fold greater affinity for cAMP than PDE4, is selectively expressed in Teff versus regulatory T (Treg) cells and controls CD4+ Teff cell adhesion and chemotaxis. Here, we determined PDE8A expression and function in CD4+ Teff cell populations in vivo. Using magnetic bead separation to purify leukocyte populations from the lung draining hilar lymph node (HLN) in a mouse model of ovalbumin-induced allergic airway disease (AAD), we found by Western immunoblot and quantitative (q)RT-PCR that PDE8A protein and gene expression are enhanced in the CD4+ T cell fraction over the course of the acute inflammatory disease and recede at the late tolerant non-inflammatory stage. To evaluate PDE8A as a potential drug target, we compared the selective and combined effects of the recently characterized highly potent PDE8-selective inhibitor PF-04957325 with the PDE4-selective inhibitor piclamilast (PICL). As previously shown, PF-04957325 suppresses T cell adhesion to endothelial cells. In contrast, we found that PICL alone increased firm T cell adhesion to endothelial cells by approximately 20% and significantly abrogated the inhibitory effect of PF-04957325 on T cell adhesion by over 50% when cells were co-exposed to PICL and PF-04957325. Despite its robust effect on T cell adhesion, PF-04957325 was over two orders of magnitude less efficient than PICL in suppressing polyclonal Teff cell proliferation, and showed no effect on cytokine gene expression in these cells. More importantly, PDE8 inhibition did not suppress proliferation and cytokine production of myelin-antigen reactive proinflammatory Teff cells in vivo and in vitro. Thus, targeting PDE8 through PF-04957325 selectively regulates Teff cell interactions with endothelial cells without marked immunosuppression of proliferation, while PDE4 inhibition has partially opposing effects. Collectively, our data identify PF-04957325 as a novel function-specific tool for the suppression of Teff cell adhesion and indicate that PDE4 and PDE8 play unique and non-redundant roles in the control of Teff cell functions.
Non-neurological major complications of extreme lateral and related lumbar interbody fusion techniques.

Background Complications exclusive of new neurological deficits/injuries that follow extreme lateral interbody fusion (XLIF) and related lateral lumbar interbody techniques should be better recognized to determine the safety of these procedures. Unfortunately, a review of the XLIF literature did not accurately reflect the frequency of these "other complications" as few US surgeons publish such adverse events that may lead to medicolegal suits. Methods Major complications occurring with XLIF included sympathectomy, major vascular injuries, bowel perforations, sterile seromas, and instrumentation failures. Results The frequency of sympathectomy was 4% for XLIF vs. 15% for anterior lumbar interbody fusion (ALIF). There were three major vascular injuries for XLIF; one fatal intraoperative event, one life-threatening retroperitoneal hematoma, and one iatrogenic lumbar artery pseudoaneurysm that was successfully embolized. Two bowel perforations were reported, whereas a third was a "direct communication." One patient developed a sterile recurrent seroma due to vancomycin powder utilized for an XLIF. One study cited malpositioning of an XLIF cage resulting in a lateral L3-L4 extrusion, whereas the second series looked at the 45% risk of cage-overhang when XLIF devices were placed in the anterior one-third of the vertebral body. Conclusion Excluding new neurological deficits, XLIF techniques resulted in multiple other major complications. However, these small numbers likely reflect just the tip of the iceberg (e.g., 10%) and the remaining 90% may never be known as many US-based spine surgeons fail to publish such adverse events as they are discoverable in a court of law and may lead to medicolegal suits.
9.12 Fluorous Linker-Enabled Organic Synthesis

Fluorous linker-enabled organic synthesis integrates the advantages of solution-phase reactions and simple phase tag-based separations. Fluorous silica gel-based solid-phase extraction and prep-LC enhanced the separation of light fluorous molecules. Applications of fluorous linkers in parallel synthesis, diversity-oriented synthesis (DOS), and mixture synthesis of small molecules and stereoisomers of natural product are presented in this chapter.
The Challenge of Primary Central Nervous System Lymphoma

Primary central nervous system (CNS) lymphoma is a challenging subtypes of aggressive non-Hodgkin lymphoma. Emerging clinical data suggest that optimized outcomes are achieved with dose-intensive CNS-penetrant chemotherapy and avoiding whole brain radiotherapy. Anti-CD20 antibody-based immunotherapy as a component of high-dose methotrexate-based induction programs may contribute to improved outcomes. An accumulation of insights into the molecular and cellular basis of disease pathogenesis is providing a foundation for the generation of molecular tools to facilitate diagnosis as well as a roadmap for integration of targeted therapy within the developing therapeutic armamentarium for this challenging brain tumor.
Adder designs using reversible logic gates

A new reversible logic gate was proposed in Ref. [1]. This gate can be used to implement any classical Boolean logic function. This paper shows the application of the reversible gate in implementing ripple carry, carry skip and carry look-ahead adders. These adders are more efficient than adders implemented using Fredkin Gates.
Clinical Examination, Duplex Ultrasound and Plethysmography for Varicose Veins:

Objective:In pursuing a policy of selective greater saphenous vein (GSV) preservation in the treatment of varicose veins we hypothesized that limbs with isolated tributary disease (TD) would be ide...
Memory access pattern based insider threat detection in big data systems

Big data platforms like Hadoop and Spark are being widely adopted both by academia and industry. In this paper, we propose a runtime intrusion detection technique that understands and works according to the memory properties of such distributed compute platforms. The proposed method is based on runtime analysis of memory access patterns of tasks running on the slave nodes of a distributed compute cluster. First, every slave node of the cluster creates a behavior profile for each task it executes. A behavior profile includes information representing the sizes of private & shared memory accesses made by a task during execution. Then, each process behavior profile is shared with other replica nodes that are scheduled to execute the same task on their copy of the same data. Next, these replica nodes verify their local tasks with the help of the information embedded in the received behavior profiles. This step is realized by running Principal Component Analysis (PCA) on the memory access patterns. Finally, nodes share their observations for consensus and report a possible intrusion to the master node if they find any discrepancy. This is a position paper and hence the proposed solution was tested and proved to work in real-time while executing the terasort mapreduce example on a small hadoop cluster.
Development of the gaseous antiparticle spectrometer for space-based antimatter detection

Abstract We report progress in developing a novel antimatter detection scheme. The gaseous antiparticle spectrometer (GAPS) identifies antimatter through the characteristic X-rays emitted by antimatter when it forms exotic atoms in gases. The approach provides large area and field of view, and excellent background rejection capability. If the GAPS concept is successfully demonstrated, then it would be an ideal candidate for space-based, indirect dark matter searches. GAPS can detect antideuterons produced in neutralino annihilations. A modest GAPS experiment can detect the neutralino for all minimal SUSY models in which the neutralino mass is in the ∼50–350 GeV mass range. Underground searches, by contrast, are only sensitive to about 1/2 the SUSY parameter space in this mass range.
Limitations on the Multiplicity of Cellular Infection During Human Alphaherpesvirus Disease

Nearly every human is persistently infected with one of three alphaherpesviruses: herpes simplex virus-1, herpes simplex virus-2, and varicella zoster virus. Infection elicits diseases ranging from epithelial lesions to viral encephalitis. Recurrent alphaherpesvirus-associated diseases result from transmission of infection from neurons. The number of viruses that productively infects a cell defines an important property known as the multiplicity of cellular infection (MOCI). The rates at which alphaherpesviruses replicate within cells, spread infection between cells, and elicit recurrent diseases are directly impacted by the MOCI. Several studies have quantified the MOCI during alphaherpesvirus infection. There is evidence that two limiting factors impact various aspects of alphaherpesvirus MOCI and directly affect pathogenesis. Those limitations include a limit on the number of viral genomes that can replicate within a host cell and a limit on cellular superinfection. This review will detail what is known about the limitations that affect MOCI and how it shapes alphaherpesvirus spread and disease.
Nurturing the Novice Writers in Psychiatric-Mental Health Nursing.

So many times colleagues or students have said to me, “I wish I could write like you,” or “Writing must come easy to you.” Equally often, they make self-deprecating comments such as “I am just not ...