cssi/SciSciGPT-SciSciNet huggingface dataset:
Regulation of hippocampal glucocorticoid receptor gene transcription and protein expression in vivo.

Glucocorticoid receptors (GRs) are glucocorticoid-activated transcription factors that modulate expression of a variety of neuronal genes. Appropriate control of GR expression is therefore critical for maintenance of cellular and organismic homeostasis. The present study assessed glucocorticoid regulation of the GR at the gene, mRNA, and protein level. Removal of circulating glucocorticoids (adrenalectomy) increased GR mRNA expression in CA1 and dentate gyrus (DG). Corticosterone (CORT) replacement normalized GR mRNA expression, whereas high doses slightly decreased GR mRNA in CA1. Parallel increases were observed using a probe complementary to the distal 3′ untranslated region, indicating that mRNA changes were not attributable to selection of alternative polyadenylation site. Expression of a GR intronic sequence was also increased by adrenalectomy, consistent with increased gene transcription. Analysis of regional GR protein expression by immunoautoradiography did not reveal changes in GR protein in pyramidal cell layers; however, increased GR signal was seen in the stratum radiatum, indicating redistribution of GR to the cytosol. Western blot analysis confirmed adrenalectomy-induced increases in hippocampal GR levels. Administration of the mineralocorticoid receptor (MR) antagonist spironolactone increased both GR mRNA and protein in CA1 and DG, consistent with MR-mediated inhibition of GR transcription. However, high-dose CORT treatment did not decrease GR mRNA or protein levels. Chronic stress exposure did not downregulate GR mRNA or protein in hippocampus. The results suggest that the hippocampal GR is subject to heterologous regulation by the MR. In contrast, GR autoregulation is only evident during prolonged exposure to high-circulating glucocorticoid levels.
Reverse saturable absorption of C 60 in liquids irradiated by picosecond and nanosecond laser pulses

Reverse saturable absorption of C60 dissolved in different solvents has been investigated under irradiation with 7-ns or 25-ps laser pulses at 532 nm. The results show that the solutions act as efficient power-limiting media under laser fluence of as high as 3 J/cm2 for both picosecond and nanosecond laser pulses. The reversely saturated (clamped) level depends on the type of solvent used. It was found that the saturated level is the lowest with carbon disulfide in comparison with several other solvents. A phenomenological model is used to describe optical limiting phenomena, including the darkening effect of C60 and the possible contribution of the solvent at high laser intensity.
Calcitonin is expressed in gonadotropes of the anterior pituitary gland: its possible role in paracrine regulation of lactotrope function

Previous studies from this laboratory have shown that salmon (S) calcitonin (CT)-like immunoreactive peptide (CTI) is synthesized and secreted by the anterior pituitary (AP) gland. These studies also co-localized CTI to gonadotropes, and demonstrated that SCT is a potent inhibitor of lactotrope function. However, the molecular structure of putative gonadotrope-derived CTI that inhibits lactotrope function has not been defined. The present studies cloned CT cDNA (pit-CT cDNA) from a mouse gonadotrope L beta T2 cell line using RT-PCR and rapid amplification of cDNA ends (RACE) techniques. Alignment of nucleotide sequences of pit-CT and mouse CT revealed greater than 99% homology between the sequences. The pit-CT cDNA was ligated into a mammalian expression vector, and the construct was transfected into L beta T2 cells. Two stable transfectant cell lines (CT.U6/A and B) were obtained by selection in G418. Subsequent S1-nuclease protection assay and immunocytochemistry results have shown that: (1) pit-CT peptide expressed by CT.U6 cell lines immunoreacted with GCT1-anti-SCT serum; (2) secretions of CT.U6 cells inhibited prolactin (PRL) release, PRL mRNA abundance and DNA synthesis of PRL-secreting GGH3 cells; and (3) CT.U6-induced inhibition was abolished by GCT1-anti-SCT serum. The studies also generated a riboprobe from the cloned pit-CT cDNA, and localized CT mRNA expression in gonadotropes of rat AP gland by in situ hybridization histochemistry. These results demonstrate that pit-CT mRNA is closely homologous to mouse CT mRNA; it is expressed by gonadotropes of the rat AP gland, and the peptide may significantly affect lactotrope function by inhibiting PRL release and cell proliferation.
Augmentation of soil detritus affects the spider community and herbivory in a soybean agroecosystem

If soil detritivores provide a significant prey source for predators in the vegetation, then augmentation of the soil community could affect the grazing food web. Specifically, increases in predator density could enhance any top-down effects and reduce herbivory. We, tested this hypothesis by providing detrital subsidies in the form of composted vegetable matter to 36 m 2 plots in soybean, Glycine max (L.) Merr. (Fabales: Fabaceae), fields that were managed using either conventional or conservation tillage practices. The foliage-dwelling spiders, insect predators, and leaf-chewing insects were censused and the body size of one large spider species, Argiope trifasciata (Forskal) (Araneae: Araneidae), was measured. In addition, the density and size of the plants were assessed and leaf amage was quantified. Any effects of treatments on the palatability of soybean plants to herbivores were determined in two laboratory experiments. Compost increased the density of foliage dwelling spiders and the abdomen size of A. trifasciata. We uncovered no treatment effects on insect predators, herbivorous insects, or plant characteristics except that compost addition reduced leaf damage. In addition, there was a negative correlation across plots between spider abundance and soybean leaf damage and abdomen width of A. trifasciata and weed herbivory levels across plots. These results suggest a connection between the soil community and the foliage food web, but the spiders appear to have exerted a top-down effect without a shift in herbivore abundance. Further study of the specific seasonality of the herbivores and their behavior in the presence of spiders are needed to uncover the underlying mechanism. Nevertheless, these results provide evidence for complex linkage between the soil and grazing food webs that may be important to biological control.
SERC/LC3R: a new paradigm for cluster-based routing in MANETs

This paper presents a new paradigm to enhance the cluster stability and support the route reliability in the cluster-based ad hoc routing protocols. This paradigm is based on providing a secondary clusterhead (SCH) for each clusterhead, which we call here primary clusterhead (PCH). This SCH, which is a regular member node, is identified and assigned by its PCH to be the future leader of the cluster. The SCH will be triggered to be the PCH when the former PCH can no longer be a clusterhead. To enhance the cluster stability, this paradigm introduces a new protocol to reform the cluster, namely the smooth and efficient re-clustering (SERC) protocol. In SERC, since the future clusterhead is known by the cluster members, the cluster leadership will be transferred smoothly and the cluster will be reformed immediately with no need to invoke the clustering algorithm. To support the route reliability, this paradigm provides a new multipath routing protocol, which is named a localized cluster-based rerouting and resource reservation protocol (LC3R). In LC3R, the main route can be established through the PCH chains, while the backup route can be established through the SCH chains. In this study, we show how the SERC/LC3R works and how this paradigm can achieve a high packet delivery rate with saving clustering and routing overhead.
CMOS diodes operating beyond avalanche frequency

This paper describes IMPATT diodes designed and fabricated in 0.25µm CMOS technology to operate beyond avalanche frequency. IMPATT Impedance measurements from 40MHz to 110GHz confirmed avalanche frequency range from 30GHz to 55GHz and negative resistance tuning range from 30GHz to 80GHz. G&H model is verified and the impact of different device parameters are presented
Systematic instruction for individuals with acquired brain injury: Results of a randomised controlled trial

The goal of this study was to evaluate experimentally systematic instruction compared with trial-and-error learning (conventional instruction) applied to assistive technology for cognition (ATC), in a double-blind, pre-test-post-test, randomised controlled trial. Twenty-nine persons with moderate-severe cognitive impairments due to acquired brain injury (15 in systematic instruction group; 14 in conventional instruction) completed the study. Both groups received 12, 45-minute individual training sessions targeting selected skills on the Palm Tungsten E2 personal digital assistant (PDA). A criterion-based assessment of PDA skills was used to evaluate accuracy, fluency/efficiency, maintenance, and generalisation of skills. There were no significant differences between groups at immediate post-test with regard to accuracy and fluency. However, significant differences emerged at 30-day follow-up in favour of systematic instruction. Furthermore, systematic instruction participants performed significantly better at immediate post-test generalising trained PDA skills when interacting with people other than the instructor. These results demonstrate that systematic instruction applied to ATC results in better skill maintenance and generalisation than trial-and-error learning for individuals with moderate-severe cognitive impairments due to acquired brain injury. Implications, study limitations, and directions for future research are discussed.
An adaptive least squares algorithm for the efficient training of artificial neural networks

A novel learning algorithm is developed for the training of multilayer feedforward neural networks, based on a modification of the Marquardt-Levenberg least-squares optimization method. The algorithm updates the input weights of each neuron in the network in an effective parallel way. An adaptive distributed selection of the convergence rate parameter is presented, using suitable optimization strategies. The algorithm has better convergence properties than the conventional backpropagation learning technique. Its performance is illustrated, using examples from digital image halftoning and logical operations such as the XOR function. >
Cognitive model exploration and optimization: a new challenge for computational science

Parameter space exploration is a common problem tackled on large-scale computational resources. The most common technique, a full combinatorial mesh, is robust but scales poorly to the computational demands of complex models with higher dimensional spaces. Such models are routinely found in the modeling and simulation community. To alleviate the computational requirements, I have implemented two parallelized intelligent search and exploration algorithms: one based on adaptive mesh refinement and the other on regression trees. These algorithms were chosen because there is a dual interest in approaches that allow searching a parameter space for optimal values, as well as exploring the overall space in general. Both intelligent algorithms reduce computational costs at some expense to the quality of results, yet the regression tree approach was orders of magnitude faster than the other methodologies.
STRESSES AROUND FLEXIBLE ELLIPTIC PIPES

Experimental and finite element techniques are used to study the effect of such factors as interface slippage on the elastic soil-structure interaction of long-span, flexible, elliptic culverts and underpasses. The two-dimensional analyses of both a deeply buried pipe under distributed loading and a shallow conduit under concentrated loading indicate that the soil can be the basic load-supporting component of the system, as has been observed earlier for circular pipes. The experimental work is possibly the first application of the combined holographic-interferometric and photoelastic approach to a practical civil engineering problem.
Backtracking without trailing in CLP (RLin)

Constraint logic programming (CLP) is a generalization of logic programming where unification is replaced by constraint solving as the basic operation of the language. The combination of constraint solving and nondeterminism (approximated by backtracking) makes these languages appealing for a variety of combinatorial search problems. Existing CLP languages support backtracking by generalizing traditional Prolog implementations: modifications to the constraint system are trailed and restored on backtracking. Although simple and efficient, trailing may be very demanding in memory space, since the constraint system may potentially be saved at each choice point. This paper proposes a fundamentally new implementation scheme for backtracking in CLP languages over linear (rational or real) arithmetic. The new scheme, called semantic backtracking, does not use trailing but rather exploits the semantics of the constraints to undo the effect of newly added constraints. Semantic backtracking reduces the space complexity by an order of magnitude compared to implementations based on trailing and makes space complexity essentially independent of the number of choice points. In addition, semantic backtracking introduces negligible space and time overhead on deterministic programs. The price for this improvement is an increase in backtracking time, although constraint-solving time may actually decrease. The scheme has been implemented as part of a complete CLP system CLP(RLin) and compared analytically and experimentally with an optimized trailing implementation. Experimental results indicate that semantic backtracking produces significant reduction in memory space, while keeping the time overhead reasonably small.
Uni‐ and multidimensional identification of rise time, spectral slope, and cutoff frequency

Absolute identification of rise time, spectral slope, and cutoff frequency was evaluated using complex tones comprising the first 40 harmonics of 200 Hz. Ranges of each dimension were restricted to those with relevance to natural music and speech. Baseline unidimensional fixed‐background tasks yielded 1.5–2.0 bits of information, indicating that listeners could consistently identify at least three to four categories per dimension. Fixed‐and roved‐background information transfers implied rise time was perceptually separable from the other dimensions. Spectral slope and cutoff frequency displayed substantial integrality (ratios of fixed‐background to roved‐background information transfers of 1.08–5.03), but the extent decreased with experience (retest ratios of 1.03–2.64). Stimulus combinations that maximized differences in high‐frequency spectral regions were associated with increased information transfer and greater separability, suggesting a functional role for ‘‘sharpness’’ in timbre identifications. Total multidimensional information transfer was closely approximated by the sum of the corresponding unidimensional roved‐background values, supporting both the general additivity of information transfer and the feasibility of using unidimensional roved‐background tasks to estimate multidimensional resolution efficiently.
New vaccines against tuberculosis. The status of current research

The increasing realization that the current vaccine for tuberculosis, bacille Calmette-Guerin (BCG), is of varying effectiveness, and is less protective in adults than in children, has prompted new research for a replacement. New research has resulted in innovative approaches, including the use of sub-unit vaccines, auxotropic vaccines, DNA vaccines, and recombinant vaccines, among others. This article reviews these approaches and test results in animal models, and discusses their potential for use in humans.
PROSTATE CANCER IN A LARGE PROSTATE IS ASSOCIATED WITH A DECREASED PROSTATE SPECIFIC ANTIGEN FAILURE RATE AFTER BRACHYTHERAPY

ABSTRACTPurpose: A large prostate has been found to correlate with improved prostate cancer survival in men undergoing radical prostatectomy. In the current study we analyzed the relationship of prostate size and prostate specific antigen (PSA) failure in men undergoing brachytherapy for localized prostate cancer.Materials and Methods: We studied data on 613 men who had undergone 125I radioactive seed implantation. Average patient age ± SD was 65 ± 7.2 years. Average prostate volume ultrasonically measured at seed insertion was 40 ± 15 ml. All patients had a minimum of 2 years of followup.Results: Men with a large prostate had increased freedom from failure compared to men with a small prostate. Failure time in men with an intermediate size prostate was between that for large and small prostates. This difference in failure rates was significant (log rank test p = 0.0002). We further analyzed our data with Cox regression. Large prostate size significantly correlated with increased time to PSA failure (p = ...
PRESERVATION OF PROPERTIES UNDER MIXTURE

In general, finite mixtures of distributions with increasing failure rates are not increasing. However, conditions have been given by Lynch [8] so that a mixture of distributions with increasing failure rates has increasing failure rate. We establish similar results for other standard classes and also give examples which show that although the assumptions are stringent, continuous mixtures of standard families of lifetime distributions do have increasing failure rates. We also show that the result of Lynch follows from Savits [12] and the techniques of the last-cited paper can be applied to other classes as well.
Rule development process for positioning strategies in the fast changing high-technology market

A discussion is presented of how to develop adaptively a rule-based system which can provide firms with guidelines in deciding positioning strategies for their products in the fast-changing high-technology market. The rule-development and revision processes and positioning strategies are considered. The authors stress that one important issue of the rule-development process is credibility of rules developed. The methodology is applied to workstation products and is proven to be useful for decision-making in positioning strategy. Rules developed with a rule-revision process using workstation industry data up to 1987 and applied to 1988 give 91.7% prediction accuracy. >
A Multidimensional Approach to Understanding Neighborhood Schools and Their Potential Impact.

Many districts are considering revamping the systems determining which schools students attend. These discussions are, inherently, about the fate of the neighborhood school. But this term has never been well defined. We develop a three-dimensional, theoretically, and empirically grounded definition of a neighborhood school. The authors’ two case studies demonstrate that these dimensions are independent and differentially related to academic achievement. The results suggest that youth in the authors’ samples have higher academic performance when they attend school with both the majority of youth in their neighborhoods and with students from other neighborhoods. Therefore, districts interested in promoting achievement gains and promoting within-school diversity may consider a policy in which all the youth from a number of neighborhoods are placed in a single school.
Population Strategies of Cardiovascular Disease Prevention: Scientific Base, Rationale and Public Health Implications

Congruence of evidence from all medical research methodologies has established the major causal influences in cardiovascular disease. Causation thus established, epidemiological observations are the best available evidence on which to base estimates of the potential of preventive strategies. From population comparisons we learn that some countries have little cardiovascular disease; therefore, prevention is a reality. From mortality surveillance we learn that the disease processes are highly dynamic. Parallels between cardiovascular disease and major non-cardiovascular disease mortality trends suggest that they have common causes and that common preventive strategies may be effective for both. From migrant studies we learn the predominant contribution to population risk of environment and culture. From population surveys we learn that risk characteristics for cardiovascular disease are mass phenomena, therefore they require mass preventive approaches. Follow-up studies in cohorts provide evidence of the r...
What, if Anything, is Teleology? The Ambiguous History of "Purpose" in Organizational Thought:

A central point of departure of social and organizational systems theory from it origins in structural-functional sociology is the idea, drawn from cybernetic theory, that systems are, or may be interpreted as, naturally purposeful. Although the purposeful-or teleologicall" character of systems is typically defended on ostensibly scientific grounds, this paper argues that: (1) teleology has no valid status as a scientific idea, but is instead a quasi-religious, mystical belief disguised in scientific-sounding jargon; (2) the belief that the purposeful character of machine or nature may be inferred from observations of their behavior alone, rather than through reference to ordinary human intention, is logically untenable; (3) as systems theories have used the term, teleology confuses a system "way of viewing" phenomena with an assertion that they concretely exist (i.e., a confusion of an epistemological with an ontological claim), thus rendering a tautological argument that systems are purposeful; (4) by c...
Some sensing and perception techniques for an omnidirectional ground vehicle with a laser scanner

This paper presents some techniques for sensing and perception for an omnidirectional autonomous ground vehicle equipped with a laser scanner. In an assumed structured environment, the sensor data processing methods for both 1D and 2D laser scanners, are discussed. Raw data are segmented to lines, circles, ellipses, planes and corners by task dependent segmentation algorithms. Each subset of data is then used for fitting the known template shapes as listed above. An arbitrator is used to discriminate the shape for the final object identification.
INPUT-MULTIPLICITY IN LUMPED-PARAMETER SYSTEMS

Input multiplicity is a situation in which different inputs can give the same output. In this work we identify the conditions leading to input multiplicity and present an efficient technique for dividing the parameter space into regions with different number of input states as well as with different types of bifurcation diagrams. It is shown that bounds on the values of the manipulated inputs have an important impact on the number of feasible solutions. The technique is illustrated with examples.
The impact of food allergy on the daily activities of children and their families.

Background Food allergy affects a significant number of children, and its management requires considerable time and vigilance. Objective To determine the impact of food allergy on the daily activities of food allergic children and their families. Methods Caregivers of food allergic children from a university-based allergy practice completed a questionnaire that evaluated their perception of the impact of their child's food allergy on family activities. Results Of the 87 families who completed the study, more than 60% of caregivers reported that food allergy significantly affected meal preparation and 49% or more indicated that food allergy affected family social activities. Forty-one percent of parents reported a significant impact on their stress levels and 34% reported that food allergy had an impact on school attendance, with 10% choosing to home school their children because of food allergy. The number of food allergies had a significant impact on activity scores, but the existence of comorbid conditions such as asthma and atopic dermatitis did not significantly affect the results. Conclusions Food allergy has a significant effect on activities of families of food allergic children. Further study is needed to determine more detailed effects of food allergy on parent-child interactions and development.
Measurement and correlation of acoustic cavitation with cellular bioeffects.

Using broadband noise as a measure of cavitation activity, this study determined the kinetics of cavitation during sonication of Optison ® contrast agent and tested whether cellular bioeffects can be predicted by cavitation dose. Cell suspensions were exposed to ultrasound at varying acoustic frequency, pressure, exposure time, Optison ® concentration and cell type to obtain a broad range of bioeffects, i.e., intracellular uptake and loss of viability, as quantified by flow cytometry. We found that cavitation activity measured by broadband noise increased and peaked within 20 ms and then decayed with a half-life of tens to hundreds of milliseconds. Intracellular uptake and loss of viability correlated well with the cavitation dose determined by the time integral of broadband noise magnitude. These results demonstrate that broadband noise correlates with bioeffects over a broad range of experimental conditions, which suggests a noninvasive feedback method to control ultrasound's bioeffects in real time. (E-mail: prausnitz@gatech.edu) © 2006 World Federation for Ultrasound in Medicine & Biology.
CONSISTENT SPECIFICATION TESTING WITH NUISANCE PARAMETERS PRESENT ONLY UNDER THE ALTERNATIVE

The nonparametric and the nuisance parameter approaches to consistently testing statistical models are both attempts to estimate topological measures of distance between a parametric and a nonparametric fit, and neither dominates in experiments. This topological unification allows us to greatly extend the nuisance parameter approach. How and why the nuisance parameter approach works and how it can be extended bear closely on recent developments in artificial neural networks. Statistical content is provided by viewing specification tests with nuisance parameters as tests of hypotheses about Banach-valued random elements and applying the Banach central limit theorem and law of iterated logarithm, leading to simple procedures that can be used as a guide to when computationally more elaborate procedures may be warranted.
The Rural Settlement History of the Hector Backbone

As discussed in the preceding article, this volume details a research project conducted by graduate students at New York University and Columbia University intended to construct and use a GIS-based database to analyze the lifeways and history of rural farmers who occupied the Hector. Backbone during the 19th and early-20th centuries. In order to establish a context within which the remainder of this yolume can be understood, this article pro­ vid'es a general historical outline of the region. This historical outline will consist of a dis­ cussion of four rather broadly defined succes­ sive periods: 1) Conquest and pioneer settle­ ment, ca. 1775-1800; 2) Settlement and agricul­ tural "boom", ca. 1800-1865; 3) Economic and population decline, ca. 1865-1900; and 4) Rural abandonment and federal management, ca. 1900-present. The time spans into which these periods are divided are not based on specific historic events and should not be considered rigid or binding. Rather, these periods were chosen as a way to meaningfully discuss the major trends and events relevant to the study area in the 19th and early-20th centuries. Providing a cursory overview of these periods for the Finger Lakes region is necessary so that the archaeological and historical data described in this volume can be better under­ stood and interpreted.
Thermally Stable Silver Nanowire–Polyimide Transparent Electrode Based on Atomic Layer Deposition of Zinc Oxide on Silver Nanowires

The performance of a flexible transparent conductive electrode with extremely smooth topography capable of withstanding thermal processing at 300 °C for at least 6 h with little change in sheet resistance and optical clarity is reported. In depth investigation is performed on atomic layer deposition (ALD) deposited ZnO on Ag nanowires (NWs) with regard to thermal and atmospheric corrosion stability. The ZnO coated nanowire networks are embedded within the surface of a polyimide matrix, and the <2 nm roughness freestanding ­electrode is used to fabricate a white polymer light emitting diode (PLED). PLEDs obtained using the ZnO-AgNW-polyimide substrate exhibit comparable performance to indium tin oxide (ITO)/glass based devices, verifying its efficacy for use in optoelectronic devices requiring high processing temperatures.
Bayesian analysis of two-piece location-scale models under reference priors with partial information

Bayesian estimators are developed and compared with the maximum likelihood estimators for the two-piece location-scale models, which contain several well-known distributions such as the asymmetric Laplace distribution, the two-piece normal distribution, and the two-piece Student- t distribution. For the validity of Bayesian analysis, it is essential to use priors that could lead to proper posterior distributions. Specifically, reference priors with partial information have been considered. A sufficient and necessary condition is established to guarantee the propriety of the posterior distribution under a general class of priors. The performance of the proposed approach is illustrated through extensive simulation studies and real data analysis.
Meaning of Illness and Cardiovascular Risk Factors in Patients With Type 2 Diabetes

PurposeThe purpose of this study was to examine the relationship between meaning of illness and cardiovascular disease risk factors in patients with type 2 diabetes.MethodsThe sample population was recruited from primary care clinics in the southeastern United States. The meaning of illness was assessed by a validated questionnaire with 5 subscales. The primary outcomes were cardiovascular disease (CVD) risk factors, assessed by A1C, systolic and diastolic blood pressure (SBP and DBP, respectively), and low-density lipoprotein cholesterol (LDL-C). Multivariate linear regression models investigated associations between the clinical outcomes and the 5 MIQ factors, controlling for possible confounders.ResultsThe sample comprised 302 black and white participants of whom more than half were elderly (65+ years) and the vast majority were male (98%). Systolic blood pressure was positively associated with non-anticipated vulnerability. Diastolic blood pressure was negatively associated with degree of stress/chang...
Infrared Image Processing for Operating Point Control of Gas Turbine Combustor

The paper presents a technique to estimate the combustor equivalence ratio based on broadband infrared flame images. A static zonal interrogation technique was developed to separate flame images from the combustor background. Histogram characteristics of gray scale images were used to correlate the image properties with flame equivalence ratios. Two histogram properties i.e. average number of pixels at 100 to 200 intensity-class and number of pixels at 150 intensity-classes were used to develop the correlation.Copyright © 2004 by ASME
Insights into the photochemical disproportionation of transition metal dimers on the picosecond time scale.

The reactivity of five transition metal dimers toward photochemical, in-solvent-cage disproportionation has been investigated using picosecond time-resolved infrared spectroscopy. Previous ultrafast studies on [CpW(CO)3]2 established the role of an in-cage disproportionation mechanism involving electron transfer between 17- and 19-electron radicals prior to diffusion out of the solvent cage. New results from time-resolved infrared studies reveal that the identity of the transition metal complex dictates whether the in-cage disproportionation mechanism can take place, as well as the more fundamental issue of whether 19-electron intermediates are able to form on the picosecond time scale. Significantly, the in-cage disproportionation mechanism observed previously for the tungsten dimer does not characterize the reactivity of four out of the five transition metal dimers in this study. The differences in the ability to form 19-electron intermediates are interpreted either in terms of differences in the 17/19-...
Abstract A259: Characterization of next generation (Gen2.5) KRAS antisense inhibitors in NSCLC, PDAC, and CRC models.

KRAS is among the first described oncogenes and one of the most frequently mutated genes in human solid tumors. Despite substantial efforts to identify specific KRAS inhibitors, no effective therapeutic strategies to target KRAS directly have been identified. Here we describe the selective inhibition of KRAS with next generation (Gen2.5) antisense oligonucleotides. We recently demonstrated preclinical and clinical activity of a next-generation constrained-ethyl (cEt) modified (Gen 2.5) antisense oligonucleotides (ASOs) targeting STAT3 mRNA (STAT3Rx/AZD9150). Systemic delivery of unformulated STAT3Rx/AZD9150 produced robust target RNA and protein reductions in a broad range of xenograft models (AACR 2013). More importantly, STAT3Rx/AZD9150 showed striking clinical activity in the phase I dose escalation study, producing anti-tumor activity in 4 out of 6 patients with advanced treatment-refractory lymphoma (ASCO 2013). In this study, we generated a panel of high affinity Gen2.5 ASO targeting KRAS. Anti-proliferative effects of the KRAS ASOs were evaluated on a panel of colorectal carcinoma (CRC), non-small cell lung carcinoma (NSCLC) and pancreatic ductal adenocarcinoma (PDAC) cell lines. KRAS ASOs potently and selectively inhibited growth of KRAS mutant CRC lines but did not affect the growth of KRAS WT CRC cells in 2D growth assays. Evaluation of KRAS depletion in NSCLC and PDAC lines revealed that sensitivity of these lines to growth inhibition in 2D assays required mutant KRAS status and the presence of a previously described “KRAS addiction” gene expression signature (Singh et al 2009). Surprisingly, further evaluation of KRAS ASO mediated depletion of NSCLC and PDAC lines in 3D growth assays (e.g. soft agar colony formation and polystyrene sponge (Alvetex)) resulted in strong inhibition of colony formation in all mutant KRAS lines, but not WT KRAS lines, and the sensitivity to KRAS depletion was independent of the expression of the “KRAS addiction” signature. Collectively, we have shown that KRAS mutational status confers specific sensitivity to the ASO-mediated KRAS knockdown (KRAS oncogene addiction). Our data also highlights that antisense-mediated inhibition of KRAS may represent a promising and translatable approach to target KRAS therapeutically. Citation Information: Mol Cancer Ther 2013;12(11 Suppl):A259. Citation Format: Alexey S. Revenko, Gourab Bhattachrjee, Chris May, Brett P. Monia, A. Robert MacLeod. Characterization of next generation (Gen2.5) KRAS antisense inhibitors in NSCLC, PDAC, and CRC models. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2013 Oct 19-23; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2013;12(11 Suppl):Abstract nr A259.
Use of Axillary Cannulation for Simultaneous Endo-Occlusion and Antegrade Perfusion during Minimally Invasive Surgery:

OBJECTIVE We aimed to develop an antegrade arterial perfusion method that would allow a single suture line on the heart. METHODS Using an 8-mm Dacron graft sewn to the right axillary artery, we performed antegrade arterial flow and simultaneous endo-occlusion, as well as the delivery of antegrade cardioplegia. RESULTS Five patients underwent right axillary antegrade flow, with intention to use axillary endo-occlusion. There were no deaths, axillary artery injuries, or conversions to sternotomy. One patient who had a small (6 mm) axillary artery required femoral arterial balloon placement with axillary arterial flow. When using a 100-mm endoballoon, transesophageal echo alone is suitable for placement of the endoballoon. All patients are alive and doing well at least 1 year after surgery. CONCLUSIONS The right axillary artery is a suitable conduit for simultaneous endo-occlusion, antegrade flow, and antegrade cardioplegia delivery during mitral valve surgery.
Subclavian flap repair after mycotic aneurysm of patch repair of coarctation.

A mycotic aneurysm developed at the site of Dacron patch repair of coarctation in a young adult. The resultant aorto-bronchial fistula was successfully managed by subclavian flap repair.
A week in Havana, Cuba, in February 2015.

In late 2014, I received an invitation from MEDICC (Medical Education Cooperation with Cuba), a nonprofit organization founded in 1997 that works to enhance cooperation among the US, Cuban, and global health communities through its programs, to be part of a delegation of 13 editors of various US medical journals to visit Cuba in February 2015. I jumped at the invitation, and it proved to be a busy, educational, and enjoyable 7 days.
Angola and Cambodia 1991–1993

This chapter will analyze the UN’s disarmament processes conducted in Angola and Cambodia between 1991 and 1993. Despite the concurrence of these operations the UN’s commitments to each could hardly have been more contrasting. On the one hand, the United Nations Transitional Authority in Cambodia (UNTAC) involved the deployment of over 22,000 military and civilian personnel, consequently making it the largest UN peacekeeping operation to date. On the other, the second United Nations Angolan Verification Mission (UNAVEM II) was to consist of only 350 military observers, 90 police monitors and 400 civilian election observers. Commensurately, whilst UNTAC’s operational budget exceeded $2 billion, UNAVEM II was forced to cope with only $132 million.
Lock-and-key dimerization in dense Brownian systems of hard annular sector particles.

We develop a translational-rotational cage model that describes the behavior of dense two-dimensional (2D) Brownian systems of hard annular sector particles (ASPs), resembling C shapes. At high particle densities, pairs of ASPs can form mutually interdigitating lock-and-key dimers. This cage model considers either one or two mobile central ASPs which can translate and rotate within a static cage of surrounding ASPs that mimics the system's average local structure and density. By comparing with recent measurements made on dispersions of microscale lithographic ASPs [P. Y. Wang and T. G. Mason, J. Am. Chem. Soc. 137, 15308 (2015)], we show that mobile two-particle predictions of the probability of dimerization ${P}_{\mathrm{dimer}}$, equilibrium constant $K$, and 2D osmotic pressure ${\mathrm{\ensuremath{\Pi}}}_{2\mathrm{D}}$ as a function of the particle area fraction ${\ensuremath{\phi}}_{\mathrm{A}}$ correspond closely to these experiments. By contrast, predictions based on only a single mobile particle do not agree well with either the two-particle predictions or the experimental data. Thus, we show that collective entropy can play an essential role in the behavior of dense Brownian systems composed of nontrivial hard shapes, such as ASPs.
A Deviation Flow Refueling Location Model for Continuous Space: A Commercial Drone Delivery System for Urban Areas

Drones, which refer to a range of small-sized unmanned aerial vehicles propelled by multiple rotors, recently have been utilized for various purposes, such as military, surveillance, photography, and entertainment. Delivery service for small products is one of their potential applications, and optimal path planning is essential for operational efficiency of such a delivery service. Because a drone’s movement is not limited to existing transportation networks, path planning needs to be conducted in continuous space while taking into account obstacles for flight. However, due to the limited flight range of battery-powered drones, multiple recharging stations are required in large urban areas to complete delivery without running out of power. In this chapter, we present a new coverage model that can optimize the location of recharging stations for delivery drones as well as ensure construction of a feasible delivery network that connects the stations and covered demand based on continuous space shortest paths. A heuristic solution technique is utilized for the optimization of station locations. Application results show the effectiveness of our model for construction of a drone delivery network that covers a large urban area.
Distributed Asynchronous Relaxation Methods for Linear Network Flow Problems

Abstract We consider a recently proposed, massively parallelizable algorithm [3]- [5] for the minimum cost network flow problem. The algorithm solves a dual problem which is unconstrained, piecewise linear, and involves a dual variable for each node. At each iteration a single node is chosen, and its dual variable and incident arc flows are changed in an attempt to improve the dual cost, as in Gauss-Seidel relaxation methods. In a distributed implementation, each node is a processor adjusting its own dual variable on the basis of local information communicated by adjacent nodes. We show finite convergence of a totally asynchronous (chaotic), distributed version of the algorithm in which some processors compute faster than others, some processors communicate faster than others, and there can be arbitrarily large communication delays. When scaling is applied to the serial version of the algorithm, excellent polynomial complexity bounds can be obtained as first pointed out in [23], and fully established in [24], [25]. We provide an alternative scaling procedure, and we discuss some variations of the algorithm aimed at improving practical computational performance.
Devices and architectures for rapidly reconfigurable photonic switching systems

This talk will review recent work developing a scalable photonic switching platform that enables reconfiguration at the nanosecond scale, addressing innovations in device design, packaging, and architecture that can overcome scaling limitations imposed by the physical layer.
Influence of Sulfur on Acid-Mediated Enamide Formation

The acid-mediated condensation of acetamide with butanal dimethylacetal and EtSCH2CH(OMe)2, followed by dehydration, was investigated by electronic structure calculations that supported the prediction that the Z-geometry would be favored in the product. The reaction was investigated experimentally using suitably functionalized cysteine building blocks. Some side reactions and optimization of reaction conditions are reported, en route to identifying a mild, inexpensive Lewis acid that achieves a reasonable yield of (Z)-thioenamide 21 with high stereoselectivity.
A Historical Review of Avian Retrovirus Research

Avian retrovirus research began with the first transmission of chicken leukemia in 1908 by Vilhelm Ellerman and Oluf Bang (1) who demonstrated that cell suspensions and cell-free filtrates from tissues of a chicken with myeloblastosis produced a similar disease in recipient birds. Over the next 12 years eight separate virus isolations were reported from Ellerman’s laboratory and confirming experiments were described in independent investigations from three other laboratories (2). The fact that it was many years before this pioneering work gained the recognition it deserved, grew from the misunderstanding, in those early years, of the true nature of leukemia. Nearly 20 years were to pass until, in the late twenties, transplantation studies in mammalian systems established that leukemic cells behaved like cancer cells (3). Indeed, because of their viral etiology, scepticism as to the relevance of avian leukemias persisted at least until 1967, when one text referred to avian and murine leukemias as “leukaemoid reactions to infection” (4). Thus, the later studies of Peyton Rous with solid chicken tumors were to be much more influential in the early years of cancer virus research.
Challenges for Older Drivers in Urban, Suburban, and Rural Settings.

Along with age-related factors, geographical settings—urban, suburban, and rural areas—also contribute to the differences in fatal crashes among older drivers. These differences in crash outcomes might be attributed to the various driving challenges faced by older drivers residing in different locations. To understand these challenges from the perspective of the older driver, a focus group study was conducted with drivers 65 and older from urban, suburban, and rural settings. Guided-group interviews were used to assess driving challenges, mobility options, opportunities for driver support systems (DSS), and alternate transportation needs. Content analysis of the interview responses resulted in four categories representing common challenges faced by older drivers across the settings: behavior of other drivers on the road, placement of road signs, reduced visibility of road signs due to age-related decline, and difficulties using in-vehicle technologies. Six categories involved location-specific challenges such as heavy traffic situations for urban and suburban drivers, and multi-destination trips for rural drivers. Countermeasures implemented by older drivers to address these challenges primarily involved route selection and avoidance. Technological advances of DSS systems provide a unique opportunity to support the information needs for route selection and avoidance preferences of drivers. Using the content analysis results, a framework was built to determine additional and modified DSS features to meet the specific challenges of older drivers in urban, suburban, and rural settings. These findings suggest that there is heterogeneity in the driving challenges and preferences of older drivers based on their location. Consequently, DSS technologies and vehicle automation need to be tailored to not only meet the driving safety and mobility needs of older drivers as a population, but also to their driving environment.
Fuzzy Choquet Integration of Deep Convolutional Neural Networks for Remote Sensing

What deep learning lacks at the moment is the heterogeneous and dynamic capabilities of the human system. In part, this is because a single architecture is not currently capable of the level of modeling and representation of the complex human system. Therefore, a heterogeneous set of pathways from sensory stimulus to cognitive function needs to be developed in a richer computational model. Herein, we explore the learning of multiple pathways–as different deep neural network architectures–coupled with appropriate data/information fusion. Specifically, we explore the advantage of data-driven optimization of fusing different deep nets–GoogleNet, CaffeNet and ResNet–at a per class (neuron) or shared weight (single data fusion across classes) fashion. In addition, we explore indices that tell us the importance of each network, how they interact and what aggregation was learned. Experiments are provided in the context of remote sensing on the UC Merced and WHU-RS19 data sets. In particular, we show that fusion is the top performer, each network is needed across the various target classes, and unique aggregations (i.e., not common operators) are learned.
Adolescent Dating Violence Among Lesbian, Gay, Bisexual, Transgender, and Questioning Youth

Abstract Research examining dating violence (DV) in nonheterosexual youth is arguably still in its infancy. Yet, mounting literature demonstrates that, compared to heterosexual and cisgender adolescents, lesbian, gay, bisexual, and transgender (LGBT) adolescents are at higher risk of physical aggression, emotional abuse, and sexual violence from dating partners. Underlying mechanisms for this increased risk are not fully understood, though evidence points to a minority stress model as a useful and theoretically grounded explanation. Research on the prevalence and negative consequences of DV among LGBT youth is reviewed, highlighting differences between subgroups. Couched within a minority stress framework, a case example is then presented highlighting both shared and unique characteristics (e.g., identity concealment, “outness” of one or both individuals, rejection from primary social supports, and lack of social resources) of DV in LGBT youth. Recommendations for future directions across community, clinical, and research domains are discussed.