cssi/SciSciGPT-SciSciNet huggingface dataset:
Abstract B223: Selective downregulation of interferon regulatory factor 4 by generation 2.5 antisense oligonucleotides induces strong apoptosis and sensitizes multiple myeloma cells to lenalidomide or bortezomib.

Despite significant advances made recently in treating multiple myeloma (MM), MM patients are often either unresponsive to or develop resistance to the standard therapies. Therefore, the disease still remains incurable and new more efficacious therapies are needed. Interferon Regulatory Factor 4 (IRF4) is a transcription factor which plays a critical role in the differentiation of normal B and T cells, and is strongly implicated in the development of hematological malignancies, especially MM. Although recent publications have pointed IRF4 as a key driver in the progression of MM, it is considered an intractable target by convention approaches. 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 describe next-generation .Gen 2.5 ASOs targeting IRF4. We first investigated whether selective downregulaion of IRF4 could lead to the death of MM cells and enhance the sensitivity of the tumor cells to the treatment of either lenalidomide or bortezomib. IRF4 ASOs administered via ‘free-uptake’, (lipid-independent) to cells growing in culture reduced IRF4 levels in a dose-dependent fashion with a concomitant strong induction of apoptosis in multiple human MM cell lines including KMS-11 and H929 cells. c-Myc, a key oncogene in MM and an immediate target gene of IRF4, also decreased significantly following IRF4 knockdown as anticipated. Importantly, MM cells were sensitive to even modest depletion of IRF4 ( Citation Information: Mol Cancer Ther 2013;12(11 Suppl):B223. Citation Format: Tianyuan Zhou, Joanna Schmidt, Ari Jerue, Minji Jo, Youngsoo Kim, A. Robert MacLeod. Selective downregulation of interferon regulatory factor 4 by generation 2.5 antisense oligonucleotides induces strong apoptosis and sensitizes multiple myeloma cells to lenalidomide or bortezomib. [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 B223.
Rheology of concentrated isotropic and anisotropic xanthan solutions: 3. Temperature dependence.

The oscillatory rheology of one rodlike and one semiflexible xanthan sample has been investigated as a function of temperature in the range of xanthan concentrations where the polymer forms a lyotropic liquid crystalline phase in aqueous NaCl solutions. Readily observed changes in the rheological observables at temperatures corresponding to phase boundaries permit construction of the biphasic chimney region of the temperature−composition phase diagram. The chimney region leans toward larger values of the polymer concentration with increasing temperature, presumably as a consequence of a reduction in the effective axial ratio of the helical polymer with increasing temperature. The results permit construction of plots of the rheological observables as a function of polymer concentration at temperatures T in the range 20 ≤ T ≤ 90 °C. Characteristic features of these curves observed at room temperature are preserved at higher temperatures, provided the xanthan double helix remains intact. The temperature depe...
Ultrasensitive Hydrogen Peroxide Biosensor Based on Enzyme Bound to Layered Nonoriented Multiwall Carbon Nanotubes/Polyelectrolyte Electrodes

A sensitive hydrogen peroxide sensor based on horseradish peroxidase covalently attached to layered nonoriented MWNTs modified electrode is presented. Cyclic voltammetry results gave quasi-reversible FeIII/FeII voltammetry. The electron transfer rate constant (ks) and Michaelis–Menten constant (KM) in pH 7 is 48.8±0.9 s−1 and 0.13±0.05 mM respectively. A linear calibration curve for hydrogen peroxide was obtained up to 120 nM under the optimized conditions with a remarkable detection limit of (S/N=3) 1.5 nM. Results suggest that the nonoriented nanotubes act as electrical conductors and may also provide large surface area facilitating facile electron transfer and excellent electrochemical catalysis.
Enhanced rates of fluid pinocytosis during exponential growth and monolayer regeneration by cultured arterial endothelial cells.

Rates of fluid pinocytosis by bovine aortic endothelial cells were measured during various manipulations of growth status in vitro. Sparsely seeded cultures grew exponentially until a confluent monolayer was formed, at which time growth slowed. This change in growth rate coincided with a decline in the rate of pinocytosis to about one-third that in the growing cultures. During the subsequent attainment of maximal cell density in the confluent monolayer, the pinocytic rate remained constant. There was close correlation between 3H-thymidine labelling indices, as measured by autoradiography, and the rates of pinocytosis. Mechanical “wounding” of the confluent monolayer resulted in cell migration and proliferation. Twenty-four hours after “wounding,” rates of pinocytosis per mg. cell protein were significantly enhanced. When regeneration of the monolayer was blocked by cytochalasin B, pinocytosis remained at the same rate as in the uninjured, confluent monolayer. These experiments support, and extend to endothelium, earlier observations that in growing cells pinocytosis proceeds at a higher rate than in non-growing, quiescent cells. Furthermore, they raise the possibility that the transendothelial transport of macromolecules such as lipoproteins by receptor-in-dependent fluid pinocytosis in vivo may be altered by the growth status of the endothelium.
Ecclesia ex Auditu A Reformed View of the Church as the Community of the Word of God

Does a church in the Reformed tradition ever express its own essence and self-understanding more clearly than when, in the liturgy, with the subtlest blend of invitation and command, the minister bids the congregation: ‘Hear the Word of God!’? Here, in dramatic, personal (but corporate) encounter between the people and God's Word — delivered first as Scripture and then expounded as proclamation — the church becomes anew what it already and always is: a community of the Word. A people are summoned into being by living, creative, divine Speech, and from their own side come into being — or better, move toward their true being — through the only appropriate response to divine Speech, namely that faith which comes by hearing (Rom. 10: 17). Our concern here is not to offer a systematic account of this Reformed understanding of the church in all its major aspects, but simply to raise a few of the hermeneutical questions involved: what does it mean for a church tradition to understand itself in these predominantly verbal and auditory categories, indeed to think of the whole encounter between God and man as occurring primarily in the mode of speech and hearing?
Behind the walls of poverty: Economically disadvantaged gifted and talented children

Almost fifty percent of our most able youth do not develop to their fullest potential. The lower socio‐economic groups represent the greatest areas of wasted talent. Due to the stigma of poverty, the economically disadvantaged child is under represented in gifted and talented programs. Children reared in poverty not only face a challenge when entering the educational system but create a challenge for educators as well. The economically disadvantaged student can no longer be ignored or dismissed as uneducable. Social workers can bring to the educational system the means through which to intervene in society's subculture of the economically disadvantaged. They can serve as catalysts in bridging the gap between the educational system, the community and individual families. Educators should call upon the social workers to work in concert to address the problems of identifying and educating the economically disadvantaged gifted and talented child.
Between Disability and Terror: Handicapped Parking Space and Homeland Security at Fenway Park

In the United States, handicapped parking spaces tether the social construction of need to the legal assurance of equality of accessibility. However in places such as Fenway Park in Boston, the threat of terror distorts the intention of these spaces by politically reconfiguring their presence and meaning. As a result, our public interest is legally manipulated and socially challenged to preference the abstraction of threat over real life in even the most ordinary of places.
Studies on the regulation of ribulose-1,5-diphosphate carboxylase synthesis during the cell cycle of the eucaryote Chlorella

Abstract The patterns of synthesis of ribulose-1,5-diphosphate carboxylase were measured in synchronous and synchronized cultures of Chlorella under conditions in which the cells divided into either 4 or 8 daughter cells. The synthesis of the carboxylase occurred in the absence of DNA replication and could be changed from a periodic to continuous pattern during the cycle by increasing the growth rate and the division number of the cells. The evidence suggests that endproduct repression might play the major role in regulating the timing of synthesis of this enzyme during the cell cycle.
Evaluating Outcomes in a Substance Abuse Training Program for Southeast Asian Human Service Workers: Problems in Measuring Change Cross-Culturally:

The following article describes the evaluation challenges faced in a cross-cultural substance abuse training program. Non-Southeast Asian instructors designed and taught courses for Cambodian and Vietnamese human service workers over a two-year period. Although cultural considerations were a central focus in the design of the program, instructors underestimated the difficulty of modifying standard questionnaires for use with Southeast Asian participants. As a consequence, the formal evaluation process had limited benefit but several insights were gleaned through alternative evaluation methods.
Using Symbolism To Enhance the School Image

Administrators who are suffering from the backlash of criticism of the educational system might consider the use of symbolism in spreading positive information about their schools, says this writer, who suggests that counselors may be the best persons to lead such an effort.
Exploring the design space for a shared-cache multiprocessor

In the near future, semiconductor technology will allow the integration of multiple processors on a chip or multichip-module (MCM). In this paper we investigate the architecture and partitioning of resources between processors and cache memory for single chip and MCM-based multiprocessors. We study the performance of a cluster-based multiprocessor architecture in which processors within a cluster are tightly coupled via a shared cluster cache for various processor-cache configurations. Our results show that for parallel applications, clustering via shared caches provides an effective mechanism for increasing the total number of processors in a system, without increasing the number of invalidations. Combining these results with cost estimates for shared cluster cache implementations leads to two conclusions: 1) For a four cluster multiprocessor with single chip clusters, two processors per cluster with a smaller cache provides higher performance and better cost/performance than a single processor with a larger cache and 2) this four cluster configuration can be scaled linearly in performance by adding processors to each cluster using MCM packaging techniques.
Electrochemical switching of lariat ethers: enhanced cation binding by one- and two-electron reduction of an anthraquinone sidearm

The first example of cation binding enhancement by electrochemical switching in a lariat ether, accomplished by one- or two-electron reduction of a quinone sidearm, is presented.
Promise of Mineralocorticoid Receptor Blockade in Asymptomatic Left Ventricular Dysfunction

Mineralocorticoid receptor blockade (MRB) has been shown to improve survival and reduce hospitalizations for heart failure (HF) in patients with chronic severe HF (New York Heart Association class III to IV) because of systolic left ventricular dysfunction1 and in patients with myocardial infarction complicated by systolic left ventricular dysfunction and HF.2 The role of MRB in patients with mild-to-moderate HF (New York Heart Association class II) because of systolic left ventricular dysfunction is currently under investigation in a large-scale prospective, randomized study (Eplerenone in Mild Patients Hospitalization And SurvIval Study in Heart Failure [EMPHASIS-HF]). MRB has also been shown to improve echocardiographic indices of diastolic function in patients with diastolic HF and is currently under investigation in a large-scale prospective, randomized study in patients with HF and preserved left ventricular function, Treatment of Preserved Cardiac function heart failure with an Aldosterone anTagonist (TOPCAT). Costello-Boerrigter et al,3 in this issue of Hypertension , shift our focus to the potential role of MRB in asymptomatic left ventricular dysfunction (ALVD). The Studies Of Left Ventricular Dysfunction (SOLVD) prevention trial …
On the Consequences of Resampling Microwave Radiometer Observations for Use in Retrieval Algorithms

Abstract How to deal with the different spatial resolutions of multifrequency satellite microwave radiometer measurements is a common problem in retrievals of cloud properties and rainfall. Data convolution and deconvolution is a common approach to resampling the measurements to a single resolution. Tropical Rainfall Measuring Mission (TRMM) Microwave Imager (TMI) measurements are resampled to the resolution of the 19-GHz field of view for use in a multifrequency optimal estimation retrieval algorithm of cloud liquid water path, total precipitable water, and wind speed. Resampling the TMI measurements is found to have a strong influence on retrievals of cloud liquid water path and a slight influence on wind speed. Beam-filling effects in the resampled brightness temperatures are shown to be responsible for the large differences between the retrievals using the TMI native resolution and resampled brightness temperatures. Synthetic retrievals are performed to test the sensitivity of the retrieved parameters...
Purification of a functional enzymatic editing complex from Trypanosoma brucei mitochondria

Kinetoplastid mitochondrial RNA editing, the insertion and deletion of U residues, is catalyzed by sequential cleavage, U addition or removal, and ligation reactions and is directed by complementary guide RNAs. We have purified a ∼20S enzymatic complex from Trypanosoma brucei mitochondria that catalyzes a complete editing reaction in vitro . This complex possesses all four activities predicted to catalyze RNA editing: gRNA‐directed endonuclease, terminal uridylyl transferase, 3′ U‐specific exonuclease, and RNA ligase. However, it does not contain other putative editing complex components: gRNA‐independent endonuclease, RNA helicase, endogenous gRNAs or pre‐mRNAs, or a 25 kDa gRNA‐binding protein. The complex is composed of eight major polypeptides, three of which represent RNA ligase. These findings identify polypeptides representing catalytic editing factors, reveal the nature of this ∼20S editing complex, and suggest a new model of editosome assembly.
Analysis of Systematic Risks in Multi-Name Credit and Equity Markets

In this paper, we present an intensity-based common factor model that is used to analyze the valuation of common systematic risks in multi-name credit and equity markets. In particular, we use a hybrid intensity model to price single-name credit instruments such as credit default swaps (CDSs), multi-name credit derivatives such as collateralized debt obligations (CDOs), and equity index options such as calls and puts on the S&P 500. Once we have the expressions for the model prices of these instruments, we then calibrate the model parameters to fit the market data. We study two problems, the “forward” and “backward” problems: in the former, we start from equity index options and then compute the CDO tranche spreads, while in the latter, we fit the parameters to the CDO tranche spreads and then compute the equity index option prices and implied volatilities. We find that, based on our hybrid model, the systematic risks in the two markets were similar from 2004 to 2007, while the credit market incorporated far greater systematic risk than the equity market during the financial crisis from 2008 to 2010.
Microstructure to substrate self-assembly using capillary forces

We have demonstrated the fluidic self-assembly of micromachined silicon parts onto silicon and quartz substrates in a preconfigured pattern with submicrometer positioning precision. Self-assembly is accomplished using photolithographically defined part and substrate binding sites that are complementary shapes of hydrophobic self-assembled monolayers. The patterned substrate is passed through a film of hydrophobic adhesive on water, causing the adhesive to selectively coat the binding sites. Next, the microscopic parts, fabricated from silicon-on-insulator wafers and ranging in size from 150/spl times/150/spl times/15 /spl mu/m/sup 3/ to 400/spl times/400/spl times/50 /spl mu/m/sup 3/, are directed toward the substrate surface under water using a pipette. Once the hydrophobic pattern on a part comes into contact with an adhesive-coated substrate binding site, shape matching occurs spontaneously due to interfacial free energy minimization. In water, capillary forces of the adhesive hold the parts in place with an alignment precision of less than 0.2 /spl mu/m. Permanent bonding of the parts onto quartz and silicon is accomplished by activating the adhesive with heat or ultraviolet light. The resulting rotational misalignment is within /spl sim/0.3/spl deg/. Using square sites, 98-part arrays have been assembled in less than 1 min with 100% yield. The general microassembly approach described here may be applied to parts ranging in size from the nano- to milliscale, and part and substrate materials including semiconductors, glass, plastics, and metals.
Light-induced electrical effects in a liquid crystal BLM containing TCNQ.

— The light-induced capacitance changes and also both photovoltage and photocurrent under continuous illumination have been investigated in pigmented liquid crystal bilayer membranes (PBLM)‡ containing TCNQ as photosensitizer with Na2SO3 electron donor on one side and methylene blue electron acceptor on the other side. The results have shown that TCNQ in cyanobiphenyl membrane produces a unique photoactive BLM system in which all three main parameters (conductivity, capacity and voltage across the membrane) are in a wide range altered by the light. It is shown that a TCNQ-cyanobiphenyl charge transfer complex is responsible for the observed photochanges. The possible mechanism of photoinduced electrical effects in this type of PBLM is discussed.
Clean intermittent catheterization as an initial management strategy provides for adequate preservation of renal function in newborns with persistent cloaca.

Summary Introduction Persistent cloaca is a rare, congenital anomaly involving the genital, urinary, and rectal organ systems. While prompt bowel diversion is the standard of care, the optimal method of genitourinary decompression is unclear. Bladder outlet obstruction and hydrometrocolpos are common complications that can lead to obstructive uropathy, abdominal distention, infection, perforation, and acidosis. Proposed management strategies include early surgical diversion (vesicostomy, vaginostomy, ureterostomy, nephrostomy) or clean intermittent catheterization (CIC) of the common channel. We hypothesized that CIC is an adequate means of genitourinary decompression and preservation of renal function, regardless of the severity of cloacal anomaly. Methods We reviewed all patients with persistent cloaca from a single, tertiary care center from 1995 to 2013. We collected data regarding renal function (serial serum creatinine prior to definitive reconstruction, and baseline estimated glomerular filtration rate [GFR]), presence of hydrocolpos, hydronephrosis, vesicoureteral reflux (VUR) or renal dysplasia, and length of the common channel. A linear mixed model was used to calculate creatinine change over time in relation to method of management and child age. Estimated GFR was calculated using the Schwartz equation for neonates = 0.45 × height in cm/serum creatinine in mg/dL. The t test was used for continuous data and Fisher's exact test was used for binomial data. A p value Results Twenty-five patients were identified. Nine (36%) patients underwent early surgical diversion versus 16 (64%) managed by CIC prior to formal reconstruction. Seven had short common channels ( Discussion Currently, there is no consensus on the initial management of obstructive uropathy and resulting hydrocolpos in newborns with persistent cloaca. In addition to CIC, management strategies include surgical options such as vesicostomy, vaginostomy, or upper tract diversions such as ureterostomy or nephrostomy. Our results suggest that CIC is similar to these other proposed diversion procedures while minimizing morbidity. Creatinine trends over time were similar between the two groups and reached comparable nadirs. Limitations of our study include the retrospective nature of a small sample size. The primary risk is differences between the two groups that we were not able to appreciate. Furthermore, we did not attempt to assess the morbidity of the two different strategies. Conclusions CIC is an adequate initial management strategy to decompress the genitourinary tract in patients with persistent cloaca. CIC preserves renal function similar to early surgical decompression.
Security relevancy analysis on the registry of Windows NT 4.0

Many security breaches are caused by inappropriate inputs, crafted by people with malicious intents. To enhance the system security, we need either to ensure that inappropriate inputs are filtered out by the program, or to ensure that only trusted people can access those inputs. In the second approach, we certainly do not want to put such a constraint on every input; instead, we only want to restrict the access to the security-relevant inputs. This paper investigates how to identify which inputs are relevant to system security. We formulate the problem as a security relevancy problem and deploy static analysis technique to identify security-relevant inputs. Our approach is based on the dependency analysis technique; it identifies whether the behavior of any security-critical action depends on a certain input. If such a dependency relationship exists, we say that the input is security-relevant, otherwise we say the input is security-nonrelevant. This technique is applied to a security analysis project initiated by the Microsoft Windows NT Security Group. The project is intended to identify security-relevant registry keys in the Windows NT operating system. The results from this approach proved useful to enhancing Windows NT security. Our experiences and results from this project are presented in this paper.
A survival‐adjusted quantal response test for comparing tumour incidence rates

Summary. The paper presents a case-study of skin fibromas among male rats in the 2-year cancer bioassay of methyleugenol that was conducted by the US National Toxicology Program (NTP). In animal carcinogenicity experiments such as this one, tumour rates are often compared with the Cochran-Armitage (CA) trend test. The operating characteristics of the CA test, however, can be adversely affected by survival differences across groups and by the assumed dose metric. Survival-adjusted generalizations of the CA test have been proposed, but they are still sensitive to the choice of scores that are assigned to the dose groups. We present an alternative test, which outperforms the survival-adjusted CA test which is currently used by the NTP to compare incidence rates. Simulated data from a wide range of realistic situations show that the operating characteristics of the test proposed are superior to those of the NTP's survival-adjusted CA test, especially for rare tumours and wide logarithmic spacings of the dose metric.
Direct binding of the quorum sensing regulator CepR of Burkholderia cenocepacia to two target promoters in vitro

Summary Burkholderia cenocepacia is an opportunistic human pathogen that can aggressively colonize the cystic fibrosis lung. This organism has a LuxR/LuxI-type quorum sensing system that enables cell–cell communication via exchange of acyl homoserine lactones (AHLs). The CepR and CepI proteins constitute a global regulatory system, controlling expression of at least 40 genes, including those controlling swarming motility and biofilm formation. In this study, we isolated seven lacZ fusions in a clinical isolate of B. cenocepacia that are inducible by octanoyl-HSL. Induction of all of these genes requires CepR. The cepI promoter was tested for induction by a set of 33 synthetic autoinducers and analogues, and was most strongly induced by long-chain AHLs lacking 3-oxo substitutions. Expression of this promoter was inhibited by high concentrations of three different autoinducers, each having six-carbon acyl chains. When CepR protein was overproduced in Escherichia coli, it accumulated in a soluble form in the presence of octanoyl-HSL, but accumulated only as insoluble inclusion bodies in its absence. Purified CepR-OHL complexes bound to specific DNA sequences at the cepI and aidA promoters with high specificity. These binding sites included a 16-nucleotide imperfect dyad symmetry. Both CepR binding sites are centred approximately 44 nucleotides upstream of the respective transcription start sites.
Downregulation of E-Cadherin enhances proliferation of head and neck cancer through transcriptional regulation of EGFR

Epidermal growth factor receptor (EGFR) has been reported to downregulate E-cadherin (E-cad); however, whether the downregulation of E-cad has any effect on EGFR expression has not been elucidated. Our previous studies have found an inverse correlation between EGFR and E-cad expression in tissue specimens of squamous cell carcinoma of the head and neck (SCCHN). To understand the biological mechanisms underlying this clinical observation, we knocked down E-cad expression utilizing E-cad siRNA in four SCCHN cell lines. It was observed that downregulation of E-cad upregulated EGFR expression compared with control siRNA-transfected cells after 72 hours. Cellular membrane localization of EGFR was also increased. Consequently, downstream signaling molecules of the EGFR signaling pathway, p-AKT, and p-ERK, were increased at 72 hours after the transfection with E-cad siRNA. Reverse transcriptase-polymerase chain reaction (RT-PCR) showed EGFR mRNA was upregulated by E-cad siRNA as early as 24 hours. In addition, RT-PCR revealed this upregulation was due to the increase of EGFR mRNA stability, but not protein stability. Sulforhodamine B (SRB) assay indicated growth of E-cad knocked down cells was enhanced up to 2-fold more than that of control siRNA-transfected cells at 72-hours post-transfection. The effect of E-cad reduction on cell proliferation was blocked by treating the E-cad siRNA-transfected cells with 1 μM of the EGFR-specific tyrosine kinase inhibitor erlotinib. Our results suggest for the first time that reduction of E-cad results in upregulation of EGFR transcriptionally. It also suggests that loss of E-cad may induce proliferation of SCCHN by activating EGFR and its downstream signaling pathways.
Broadband (0.3∼11THz) reflection spectroscopy using terahertz air photonics

Pulsed THz wave spectroscopy using air as the THz wave emitter with the excitation of femtosecond laser provides intense (>100 kV/cm) and broadband THz waves (usable bandwidth from 0.3 to 11 THz). Using the air-biased-coherent-detection (ABCD) method, air can also coherently detect pulsed THz waves over a broadband spectrum. By utilizing these two technologies, we developed a prototype THz air photonics time-domain reflection spectrometer, and applied it on many materials in normal reflection geometry. Optical properties of CaCO3 crystals and several other samples in the THz range were studied. The system provided a signal-to-noise ratio (SNR) over 1000:1, with 0.1 cm−1 frequency resolution. The results acquired from both transmission and reflection measurements were then compared.
Modeling decisions by brains that think, feel, and vegetate

This paper summarizes three interrelated neural network models of data on emotionally influenced decision making: the first on a gambling task, the second on probability judgment, and the third on probability weighting. The networks incorporate data on executive regions of the brain and organizing principles such as adaptive resonance and fuzzy traces that have been utilized to model other cognitive data.
L/sup 1/ sensitivity minimization for plants with commensurate delays

A solution is presented to the L/sup 1/ minimization problem for plants with commensurate delays. In the special case where the weight has one pole, the problem can be solved by a single linear programming problem. Other special cases are also presented. A method for computing the optimal performance and a characterization of minimizing solutions are given. >
Estimating risks to aquatic life using quantile regression

AbstractOne of the primary goals of biological assessment is to assess whether contaminants or other stressors limit the ecological potential of running waters. It is important to interpret responses to contaminants relative to other environmental factors, but necessity or convenience limit quantification of all factors that influence ecological potential. In these situations, the concept of limiting factors is useful for data interpretation. We used quantile regression to measure risks to aquatic life exposed to metals by including all regression quantiles (τ = 0.05–0.95, by increments of 0.05), not just the upper limit of density (e.g., 90th quantile). We measured population densities (individuals/0.1 m2) of 2 mayflies (Rhithrogena spp., Drunella spp.) and a caddisfly (Arctopsyche grandis), aqueous metal mixtures (Cd, Cu, Zn), and other limiting factors (basin area, site elevation, discharge, temperature) at 125 streams in Colorado. We used a model selection procedure to test which factor was most lim...
Charge trapping and low frequency noise in SOI buried oxides

We have studied the 1/f noise and total-dose response associated with the buried oxides (BOX) of fully depleted nMOS silicon-on-insulators (SOI) transistors. Silicon implantation in the BOX creates a higher density of oxygen vacancy-related defects that reduce the net oxide-trap charge, but increase the back-channel 1/f noise. The 1/f noise of MOSFETs fabricated on silicon-implanted SOI BOX shows little change after 1 Mrad(SiO/sub 2/) irradiation. Silicon implantation also creates shallow electron traps in the BOX, leading to large bias instabilities. Whether these traps are filled or empty does not significantly affect the 1/f noise. A detailed study of the 1/f noise, temperature dependence of charge trapping, and radiation response of these SOI nMOSFET transistors shows that charge exchange with shallow electron traps in the BOX occurs mostly via tunneling. Low frequency noise in the double-gate (DG) mode of device operation is also investigated, and found to help mitigate the 1/f noise in fully depleted SOI MOSFETs.
The Effect of Thermal Treatment of Hematite Ore for Chemical Looping Combustion of Methane

For chemical looping processes to become an economically viable technology, an inexpensive carrier that can endure repeated reduction and oxidation cycles needs to be identified or developed. Unfortunately, the reduction of hematite ore with methane in both batch and fluidized beds has revealed that the performance (methane conversion) decreases with time. Previous analysis had shown that the grains within the particle grew with the net effect of reducing the surface area of the particles and thereby reducing the rate and net conversion for a fixed reduction time. To improve the lifespan of hematite ore, it is hypothesized that if the grain size could be stabilized, then the conversion could be stabilized. In this work, series of tests were conducted in an electrically heated fluidized bed. The hematite ore was first pretreated at a temperature higher than the subsequent reduction temperatures. After pretreatment, the hematite ore was subjected to a series of cyclic reduction/oxidation experiments. The results show that the ore can be stabilized for cycles at different conditions up to the pretreatment temperature without any degradation. Details of the pretreatment process and the test results will be presented.
Shortening a Patient Experiences Survey for Medical Homes

The Consumer Assessment of Healthcare Providers and Systems—Patient-Centered Medical Home (CAHPS PCMH) Survey assesses patient experiences reflecting domains of care related to general patient experience (access to care, communication with providers, office staff interaction, provider rating) and PCMH-specific aspects of patient care (comprehensiveness of care, self-management support, shared decision making). The current work compares psychometric properties of the current survey and a proposed shortened version of the survey (from 52 to 26 adult survey items, from 66 to 31 child survey items). The revisions were based on initial psychometric analysis and stakeholder input regarding survey length concerns. A total of 268 practices voluntarily submitted adult surveys and 58 submitted child survey data to the National Committee for Quality Assurance in 2013. Mean unadjusted scores, practice-level item and composite reliability, and item-to-scale correlations were calculated. Results show that the shorter adult survey has lower reliability, but still it still meets general definitions of a sound survey for the adult version, and resulted in few changes to mean scores. The impact was more problematic for the pediatric version. Further testing is needed to investigate approaches to improving survey response and the relevance of survey items in informing quality improvement.
Exploring a resource dependency perspective as an organizational strategy for building resource capacity Implications for public higher education universities

Declining state revenue, increased expenditures and rising costs at public universities are critical issues that are further heightened by the current economic environment. In an effort to address the challenges associated with reduced revenue and rising costs, this theoretical paper will explore how public institutions can leverage the resource dependency theory framework for strategy formulation and increased resource capacity. The organization of the paper begins with an introduction that sets forth the topic parameters and rationale of the paper. This is followed by a literature review that provides an overview of pertinent fiscal issues and strategies that were designed to mitigate these issues in public higher education. The authors then introduce the resource dependency theory and its linkage to public higher education based upon an understanding of the institution’s interdependence with the external environment. Based upon the resource dependency theory, the authors discuss strategies that can gar...
PUBLIC ADMINISTRATION DISCOURSE A Matter of Style

This article proposes that a reorientation is required in public administration’s discourse style. It suggests that traditional style(s) cannot cope with complex problems like the ongoing antipathy against bureaucracy and bureaucracy’s “iron cage” challenges. It proposes, first, that public administration discourse should become more self-conscious about style, a feature often misunderstood as a decorative and unimportant add-on. Second, a self-conscious style should be what is described as post-ist, including emphasis on the autonomously macro and longer term. Traditional and post-ist styles are contrasted.
Engineered DNA sequence syntax inspector.

DNAs encoding polypeptides often contain design errors that cause experiments to prematurely fail. One class of design errors is incorrect or missing elements in the DNA, here termed syntax errors. We have identified three major causes of syntax errors: point mutations from sequencing or manual data entry, gene structure misannotation, and unintended open reading frames (ORFs). The Engineered DNA Sequence Syntax Inspector (EDSSI) is an online bioinformatics pipeline that checks for syntax errors through three steps. First, ORF prediction in input DNA sequences is done by GeneMark; next, homologous sequences are retrieved by BLAST, and finally, syntax errors in the protein sequence are predicted by using the SIFT algorithm. We show that the EDSSI is able to identify previously published examples of syntactical errors and also show that our indel addition to the SIFT program is 97% accurate on a test set of Escherichia coli proteins. The EDSSI is available at http://andersonlab.qb3.berkeley.edu/Software/EDSSI/.
Complex trade-offs and the evolution of starvation resistance in Drosophila melanogaster.

The measurement of trade-offs may be complicated when selection exploits multiple avenues of adaptation or multiple life-cycle stages. We surveyed 10 populations of Drosophila melanogaster selected for increased resistance to starvation for 60 generations, their paired controls, and their mutual ancestors (a total of 30 outbred populations) for evidence of physiological and life-history trade-offs that span life-cycle stages. The directly selected lines showed an impressive response to starvation selection, with mature adult females resisting starvation death 4-6 times longer than unselected controls or ancestors-up to a maximum of almost 20 days. Starvation-selected flies are already 80% more resistant to starvation death than their controls immediately upon eclosion, suggesting that a significant portion of their selection response was owing to preadult growth and acquisition of metabolites relevant to the stress. These same lines exhibited significantly longer development and lower viability in the larval and pupal stages. Weight and lipid measurements on one of the starvation-selected treatments (SB1-5), its control populations (CB1_5), and their ancestor populations (B1_5) revealed three important findings. First, starvation resistance and lipid content were linearly correlated; second, larval lipid acquisition played a major role in the evolution of adult starvation resistance; finally, increased larval growth rate and lipid acquisition had a fitness cost exacted in reduced viability and slower development. This study implicates multiple life-cycle stages in the response to selection for the stress resistance of only one stage. Our starvation-selected populations illustrate a case that may be common in nature. Patterns of genetic correlation may prove misleading unless multiple pleiotropic interconnections are resolved.
Art and Our Earthly Abode: Dewey on the Ameliorative Potential of Aesthetic Experience

Immanuel Kant and John Dewey can both plausibly be read as supporting the view that art can combat the existential Unheimlichkeit engendered by the finitude and contingency of our earthly being, and thus help us to feel more at home in the world. But, although both agree that any sense of alienation one might feel within her phenomenal existence can be transformed through the work of art, the explanation each gives for this transformative capacity betrays some important differences. Indeed, Dewey sees the contrast between himself and Kant as having to do primarily with the latter’s appeal to the infinite and non-contingent in the development of his account. In this paper, I aim to illuminate how – by taking this difference as his point of departure in explaining art’s transformative capacity – Dewey presents an equally compelling, and perhaps even more inclusive, account of how art is capable of helping us feel more at home in the world, and is one that actually places the transformative locus of the work of art within our phenomenal, contingent, and finite existence.
Separation of natural products by countercurrent chromatography

Countercurrent Chromatography (CCC) provides the natural product chemist with a high-resolution separatory method, which is uniquely applicable to sensitive (unstable) compounds and which allows virtually quantitative recovery of the load sample. Different instruments use different means of retaining a stationary liquid phase. The solvent system (SS) can be chosen to optimize the separatory power and the number of systems available is limitless. Several examples are provided to illustrate the power of the method and to guide the chemist in choice of an appropriate SS.
Single Layer Repair of Large Anterior Skull Base Defects without Vascularized Mucosal Flap.

Objectives Bilateral anterior skull base (ASB) defects following endoscopic endonasal tumor resection are most commonly repaired utilizing multilayered reconstruction with a vascularized mucosal flap. Single-layer closure of large ASB defects has been described in the literature but this technique has yet to gain a widespread use. We report our experience with a series of patients who underwent reconstruction of large ASB defects using a single-layer intradural graft, without nasoseptal flaps. We also compared the use of acellular dermal matrix (AlloDerm, LifeCell, Branchburg, New Jersey, United States) or collagen matrix xenograft (Duramatrix, Stryker, Kalamazoo, Michigan, United States) as the graft biomaterial. Design A retrospective case series. Setting Tertiary academic medical center. Main Outcome Measures Postoperative cerebrospinal fluid leak, the number of postoperative debridements, the number of postoperative infections, and time to remucosalization. Results Two patients were reconstructed with AlloDerm and three with Duramatrix, with all patients receiving postoperative external beam radiation. There were no postoperative cerebrospinal fluid leaks identified in these patients during follow-up. The AlloDerm group showed increased postsurgical crusting, the number of clinically apparent postoperative infections, and an increased time to remucosalization. Conclusions Single-layer repair without a vascularized mucosal flap is a viable method of skull base repair for large ASB defects. We found repair with Duramatrix was superior, with less graft crusting and infection, requiring fewer debridements.
The Receptor Tyrosine Kinase AXL in Cancer Progression

The AXL receptor tyrosine kinase (AXL) has emerged as a promising therapeutic target for cancer therapy. Recent studies have revealed a central role of AXL signaling in tumor proliferation, survival, stem cell phenotype, metastasis, and resistance to cancer therapy. Moreover, AXL is expressed within cellular components of the tumor microenvironment where AXL signaling contributes to the immunosuppressive and protumorigenic phenotypes. A variety of AXL inhibitors have been developed and are efficacious in preclinical studies. These agents offer new opportunities for therapeutic intervention in the prevention and treatment of advanced disease. Here we review the literature that has illuminated the cellular and molecular mechanisms by which AXL signaling promotes tumor progression and we will discuss the therapeutic potential of AXL inhibition for cancer therapy.
Implications of turbulent flow in connecting capillaries used in high performance liquid chromatography

The ongoing movement in HPLC toward the use of small columns packed with small particles for high speed separations results in eluted peaks with very small volumetric variances. Avoiding degradation of separation performance under these conditions requires careful consideration of all sources of extra-column peak dispersion. Recent trends towards decreased diameters of connecting capillaries and increased flow rates for analytical-scale separations can result in Reynolds numbers that exceed 2000. This raises the possibility of a transition from laminar to turbulent flow, thereby resulting in a higher than expected pressure drop across the capillary at a given flow rate. In this study we collected pressure drop data as a function of flow rate under many conditions relevant to modern HPLC. The variables studied included capillary diameter (50-120μm) and length (100-550mm), acetonitrile/water composition (0-100%), and temperature (20-80°C). Most of the work involved stainless steel capillaries, but a subset of experiments involved fused silica. We then used the experimental data to train a model that enables prediction of pressure drops for all of the conditions studied. We find that a single global friction factor profile is sufficient to predict pressure drops as a function of flow rate that are in qualitative agreement with the experimental results. The quantitative accuracy of these predictions is generally quite good, with a mean prediction error of about 2% over the entire range of conditions studied. Predictions for some outlying capillaries are not as good, with errors as high as -40%. This variability is probably due mainly to capillary-to-capillary variability, especially in the wall roughness, which is difficult to characterize definitively. We believe the model described here will be very useful to practicing chromatographers for predicting the conditions under which turbulent flow might develop in their connecting capillaries, and the magnitude of the pressure drop increase over that expected if flow were exclusively laminar.
From political independence to economic emancipation: reseeding Africa with entrepreneurship and institutions to accelerate economic development

AbstractA resurgence of interest in Africa in recent decades has generated an intense ideological, strategic, and pragmatic debate about the most viable strategies which could be implemented to ema...
Regional Evaluation of the Severity-Based Stroke Triage Algorithm for Emergency Medical Services Using Discrete Event Simulation.

Background and Purpose— The Severity-Based Stroke Triage Algorithm for Emergency Medical Services endorses routing patients with suspected large vessel occlusion acute ischemic strokes directly to endovascular stroke centers (ESCs). We sought to evaluate different specifications of this algorithm within a region. Methods— We developed a discrete event simulation environment to model patients with suspected stroke transported according to algorithm specifications, which varied by stroke severity screen and permissible additional transport time for routing patients to ESCs. We simulated King County, Washington, and Mecklenburg County, North Carolina, distributing patients geographically into census tracts. Transport time to the nearest hospital and ESC was estimated using traffic-based travel times. We assessed undertriage, overtriage, transport time, and the number-needed-to-route, defined as the number of patients enduring additional transport to route one large vessel occlusion patient to an ESC. Results— Undertriage was higher and overtriage was lower in King County compared with Mecklenburg County for each specification. Overtriage variation was primarily driven by screen (eg, 13%–55% in Mecklenburg County and 10%–40% in King County). Transportation time specifications beyond 20 minutes increased overtriage and decreased undertriage in King County but not Mecklenburg County. A low- versus high-specificity screen routed 3.7× more patients to ESCs. Emergency medical services spent nearly twice the time routing patients to ESCs in King County compared with Mecklenburg County. Conclusions— Our results demonstrate how discrete event simulation can facilitate informed decision making to optimize emergency medical services stroke severity-based triage algorithms. This is the first step toward developing a mature simulation to predict patient outcomes.