cssi/SciSciGPT-SciSciNet huggingface dataset:
Abstract P6-04-25: Genomic Deregulation and Therapeutic Role of Nemo-like Kinase in Luminal B Breast Cancer

Luminal B breast tumors are notoriously known as high grade breast cancer prone to Tamoxifen resistance and early recurrence. Chromosomal abnormalities are a crucial class of drug targets in cancer which can be classified into numerical and structural rearrangements. Gene amplification is the result of numerical rearrangement that generates multiple copies of an otherwise normal human gene, such as Her2 amplification observed in breast cancer. Gene fusion is the result of structural rearrangement that fuses together pieces of two different genes, such as BCR-ABL gene fusion identified in leukemia. Due to their critical role in causing human cancers and their presence exclusively in the tumor tissues, gene amplifications and fusions provide highly specific drug targets with only minimal side effects. In order to identify these chromosome aberrations that can serve as new therapeutic targets in breast cancer, we developed a novel bioinformatics analysis called “copy number signature analysis”. This is based on the observation that driving gene fusions and their original (wild-type) genes are often amplified in fusion-positive tumors, or tumors without the fusions respectively. This suggests that gene fusions and amplifications may synergize to activate important oncogenes; if directly druggable, these aberrations will provide substantial opportunities for new therapies. Applying this analysis to the newly emerged genomic data from the Cancer Genome Atlas (TCGA) project nominated Nemo-like kinase ( NLK ) as a lead therapeutic target for invasive breast cancer. NLK encodes a serine-threonine mitogen activated protein kinase that plays a pivotal role in transforming growth factor beta pathway and embryo development. Genomic amplifications and rearrangements at NLK locus happen in 7%–9% of breast tumors, which may lead to deregulated serine-threonine kinase activity. Of note, these aberrations preferentially present in luminal B or Her2 positive breast tumors, suggesting their association with these high grade tumors. Most interestingly, transient inhibition of NLK through small RNA interference in multiple breast cancer cell lines harboring NLK deregulations, we observed potent inhibition of cell growth and capability of forming tumor-like colonies, as well as increased sensitivity to Tamoxifen treatment. These data suggest that NLK might be deregulated by genetic events which may promote growth-factor signaling and Tamoxifen resistant phenotype. Molecular assays detecting NLK chromosomal aberrations may serve as a predictive biomarker for endocrine resistance in breast cancer as well as selection of patients for appropriate treatment. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P6-04-25.
Synthesis, Properties, and Application of New Luminescent Polymers with Both Hole and Electron Injection Abilities for Light-Emitting Devices

New luminescent polymers that contain both electron-withdrawing cyano groups and electron-rich moieties, triphenylamine (TPA) or tetraphenyldiaminobiphenyl (TPD), were synthesized by Knoevenagel condensation of 1,4-bis(cyanomethyl)-2-[(2-ethylhexyl)oxy]-5-methoxybenzene with the dialdehyde of TPA or TPD, respectively. The polymers were characterized by NMR, FT-IR, microanalysis, GPC, DSC, and TGA. Efficient orange photoluminescence was observed with an absolute quantum efficiency of 48% for the TPA incorporated polymer (TPA-CNPPV). Cyclic voltammetry investigation showed that the polymers presented reversible oxidation and reduction with relatively low potentials, which suggested that the polymers have both good electron and hole injection abilities. We demonstrated an effective approach to synthesize polymers with the triad properties of efficient photoluminescence, good hole injection and high electron-affinity properties, which are highly desirable for application in light-emitting devices. This point ...
The Use of Activated Recombinant Factor VII in a Patient with Fulminant Hepatic Failure Requiring Placement of an Intracranial Pressure Monitor

Objective:To evaluate the use of recombinant activated factor VII (rFVIIa) in a patient with fulminant hepatic failure (FHF) requiring placement of an intracranial pressure monitor.Case Summary:A 21-year-old female with no significant medical history was admitted to an outside hospital with elevated results of liver function tests. Subsequently, the patient was diagnosed with autoimmune hepatitis. Systemic corticosteroids were started, but her condition continued to decompensate. She was transferred to our tertiary care facility 5 days after initial presentation. The liver function test results remained elevated (eg, total bilirubin 27 mg/dL), and international normalized ratio (INR) was 3.57. The medical team decided to place an intracranial pressure monitor, with the neurosurgery team's goal being an INR less than 1.5 before placement of the monitor. After multiple units of fresh frozen plasma (FFP) failed to lower the patient's INR, rFVIIa 40 μg/kg was administered. A rapid decrease of the INR allowed ...
Optical oscillator strengths for isoelectronic ions of nitrogen

An analytic atomic active electron model potential adjusted to experimental single-particle energy levels is used to generate wave functions for the valence and excited states of O1+, F2+, Ne3+, Na4+, and Mg5+. Using these wave functions in conjunction with the Born approximation and the LS-coupling scheme, we calculate optical oscillator strengths for excitations from the 1s22s22p3(4S3/2) ground state. The results are compared to experimental data and other calculations. Systematic trends along the isoelectronic sequence are discussed.
Comparative Petrotectonic Study of Five Eurasian Ultrahigh-Pressure Metamorphic Complexes

The Dabie-Sulu belt of east-central China, the Kokchetav Complex of northern Kazakhstan, the Maksyutov Complex of the southern Urals, the Dora Maira Massif of the Western Alps, and the Western Gneiss Region of southwestern Norway all contain mineralogic/textural relics indicating the presence or earlier occurrence of coesite and/or diamond. Other ultrahighpressure phases, including K-rich clinopyroxene, Mgrich garnet, ellenbergerite, lawsonite, zoisite, glaucophane, and associations such as magnesite + diopside, talc + kyanite, diopside, high-silica phengite, and/or jadeite, also attest to metamorphic pressures approaching or even exceeding 25 to 30 kbar. Subduction zones constitute the only known plate-tectonic environment where such P-T conditions exist. Many of these UHP relics occur as tiny inclusions encased in dense, refractory, unreactive mineralogic hosts, and hence were preserved during return transit toward normal P-T conditions characteristic of midcrustal levels. Each of the exhumed ultrahigh-...
SKEPTICISM AND PERCEPTUAL CONTENT

Critique de la conception internaliste et fondationnaliste de la justification du contenu subjectif des croyances developpee par P. Moser dans son ouvrage intitule «Knowledge and evidence» (1989). Examinant la relation entre l'explication, l'experience perceptive, la proposition et le caractere non-conceptuel du contenu subjectif, l'A. montre que l'hypothese realiste defendue par Moser ne constitue pas une reponse pertinente a l'hypothese (sceptique) humeenne
An Oral History of First-Generation Leaders in Education of Children With Emotional/Behavioral Disorders, Part 3 The Future

In this the third part of an oral history of education of students with emotional and behavioral disorders, 15 first-generation leaders were asked to forecast the future of the field and to advise persons entering the profession. Their videotaped conversations were transcribed, were analyzed, and are reported here together with some discussion of apparent themes. They forecast a mixed, and sometimes discouraging, future of the field and believe that the challenges and frustrations they encountered will continue and become even greater. Although they recognize that prevention and early intervention are the best intervention, they are not optimistic about society’s willingness to invest in policies that promote prevention. Despite the challenges, they believe that the work is important, rewarding, and even fun. They encourage people to join the profession with realistic understandings of the children, conditions, roles, and challenges they will encounter and a willingness to find and cultivate professional ...
Distinct Requirements of MicroRNAs in NK Cell Activation, Survival, and Function

MicroRNAs (miRNAs) are small noncoding RNAs that have recently emerged as critical regulators of gene expression within the immune system. In this study, we used mice with conditional deletion of Dicer and DiGeorge syndrome critical region 8 (Dgcr8) to dissect the roles of miRNAs in NK cell activation, survival, and function during viral infection. We developed a system for deletion of either Dicer or Dgcr8 in peripheral NK cells via drug-induced Cre activity. We found that Dicer- and Dgcr8-deficient NK cells were significantly impaired in survival and turnover, and had impaired function of the ITAM-containing activating NK cell receptors. We further demonstrated that both Dicer- and Dgcr8-dependent pathways were indispensable for the expansion of Ly49H(+) NK cells during mouse cytomegalovirus infection. Our data indicate similar phenotypes for Dicer- and Dgcr8-deficient NK cells, which strongly suggest that these processes are regulated by miRNAs. Thus, our findings indicate a critical role for miRNAs in controlling NK cell homeostasis and effector function, with implications for miRNAs regulating diverse aspects of NK cell biology.
Scaling limits of resistive memories

This paper is intended to provide an expository, physics-based, framework for the estimation of the performance potential and physical scaling limits of resistive memory. The approach taken seeks to provide physical insights into those parameters and physical effects that define device performance and scaling properties. The mechanisms of resistive switching are based on atomic rearrangements in a material. The three model cases are: (1) formation of a continuous conductive path between two electrodes within an insulating matrix, (2) formation of a discontinuous path of conductive atoms between two electrodes within an insulating matrix and (3) rearrangement of charged defects/impurities near the interface between the semiconductor matrix and an electrode, resulting in contact resistance changes. The authors argue that these three model mechanisms or their combinations are representative of the operation of all known resistive memories. The central question addressed in this paper is: what is the smallest volume of matter needed for resistive memory? The two related tasks explored in this paper are: (i) resistance changes due to addition or removal of a few atoms and (ii) stability of a few-atom system.
Extra-amniotic balloon for preinduction cervical ripening: a randomized comparison of weighted traction versus unweighted

Objective: To determine whether a weighted versus unweighted balloon catheter achieved a shorter first stage of labor. Methods: This was a randomized trial of patients undergoing induction with Bishop score <4. Women were randomized to weighted balloon catheter with 1000 mL fluid bag or unweighted catheter taped to the thigh. Results: A total of 60 women were randomized. The time from balloon catheter insertion until discontinuation was significantly longer in the unweighted group 4.62 ± 0.65 h versus 1.59 ± 0.2 h in the weighted group (p = 0.001). This resulted in longer cervical ripening/first stage of labor in the unweighted (18.52 ± 0.96 h) versus weighted group (15.3 ± 0.99 h) (p = 0.025). The unweighted balloon catheter had a shorter first stage of labor as gravidity increased (p = 0.007) and as race went from white to non-white (p = 0.003). There was no difference in perceived pain after balloon insertion (p = 0.0942), or Bishop score after balloon discontinuation (p = 0.1661). Conclusion: The tota...
Distinct Clinical and Laboratory Activity of Two Recombinant Interleukin-2 Preparations

Interleukin-2 (IL-2) is a potent lymphokine that activates natural killer cells, T cells, and other cells of the immune system. Several distinct recombinant human IL-2 preparations have shown antitumor activity, particularly for renal cell cancer and melanoma. Somewhat distinct immune and clinical effects have been noted when different IL-2 preparations have been tested clinically; however, the regimens and doses used were not identical. To compare these more directly, we have evaluated two clinical recombinant IL-2 preparations in vitro and in vivo using similar regimens and similar IUs of IL-2. We used the Food and Drug Administration-approved, commercially available Chiron IL-2 and the Hoffmann LaRoche (HLR) IL-2 supplied by the National Cancer Institute. Using equivalent IUs of IL-2, we noted quantitative differences in vitro and in vivo in the IL-2 activity of these two preparations. In patients receiving comparable IUs of the two preparations, HLR IL-2 induced the release of more soluble IL-2 receptor α into the serum than Chiron IL-2. In addition, more toxicities were noted in patients receiving 1.5 × 10 6 IU of HLR IL-2 than were seen in patients treated with 1.5 × 10 6 or even 4.5 × 10 6 IU of Chiron IL-2. These toxicities included fever, nausea and vomiting, and hepatic toxicity. In vitro proliferative assays using IL-2-dependent human and murine cell lines indicated that the IU of HLR IL-2 was more effective than Chiron IL-2 at inducing tritiated thymidine incorporation. Using flow cytometry, we also found quantitative differences in the ability of these two preparations to bind to IL-2 receptors. These findings indicate that ∼3–6 IU of Chiron IL-2 are required to induce the same biological effect as 1 IU of HLR IL-2.
Evolution of battery-powered, vented left ventricular assist devices

Battery-powered, vented left ventricular assist devices are designed to provide long-term circulatory support and an enhanced quality of life. Their ongoing evolution into an effective clinical tool to treat patients with severe heart failure has resulted from the efforts of many, the open communication among researchers involved in the program, and the strong support from the National Institutes of Health.
Comparing Fractional Anisotropy in Patients With Childhood-Onset Schizophrenia, Their Healthy Siblings, and Normal Volunteers Through DTI

Background: Diffusion tensor imaging is a neuroimaging method that quantifies white matter (WM) integrity and brain connectivity based on the diffusion of water in the brain. White matter has been hypothesized to be of great importance in the development of schizophrenia as part of the dysconnectivity model. Childhood-onset schizophrenia (COS), is a rare, severe form of the illness that resembles poor outcome adult-onset schizophrenia. We hypothesized that COS would be associated with WM abnormalities relative to a sample of controls.
Quantifying direct vs. indirect effects of nectar robbers on male and female components of plant fitness

Summary Plants interact simultaneously with both mutualists and antagonists. While webs of plant–animal interactions in natural systems can be highly complex, most interactions can be simplified into those that are either direct (mediated through pairwise interactions) or indirect (mediated through third-party species). Mechanistic studies of the direct and indirect pathways by which foliar herbivores affect plants have been well explored; however, mechanistic explorations of how floral herbivores, such as nectar robbers, affect total plant fitness via direct vs. indirect pathways have received less attention. The goal of this study was to assess the importance of direct vs. pollinator-mediated indirect effects of a floral antagonist on female and male components of plant fitness. We focused on the hummingbird-pollinated plant scarlet gilia, Ipomopsis aggregata, which is nectar-robbed by the bumblebee Bombus occidentalis. Prior studies have found evidence for pollinator-mediated indirect effects of robbing on female and male components of I. aggregata fitness, but the mechanisms by which these indirect effects occur, and experimental evidence supporting or refuting direct effects of robbing, have been lacking. We found no evidence for direct effects of robbing on plant fitness. Robbers did not act as pollinators of I. aggregata nor did they directly affect seed production by making nectar-robber holes or removing nectar in hand-pollinated flowers. Moreover, robbing had no direct effect on pollen production per flower or the ability of pollen from robbed flowers to sire seeds in hand pollinations. However, nectar robbing had indirect effects on plant reproduction mediated through per-visit pollinator effectiveness at depositing pollen in robbed vs. unrobbed flowers. A simple model of a plant-robber-pollinator system suggested that robbing effects in general may occur through more indirect mechanisms when nectar removal by robbers is high relative to nectar replenishment, and that compensation for robbing is then more profitable through the production of additional flowers. Synthesis. Our results highlight the importance of indirect effects in mediating the fitness consequences of species interactions.
Theranostic probe for simultaneous in vivo photoacoustic imaging and confined photothermolysis by pulsed laser at 1064 nm in 4T1 breast cancer model

Here, we report that polyethylene glycol (PEG)-coated copper(II) sulfide nanoparticles (PEG-CuS NPs) with their peak absorption tuned to 1064 nm could be used both as a contrast agent for photoacoustic tomographic imaging of mouse tumor vasculature and as a mediator for confined photothermolysis of tumor cells in an orthotopic syngeneic 4T1 breast tumor model. PEG-CuS NPs showed stronger photoacoustic signal than hollow gold nanospheres and single-wall carbon nanotubes at 1064 nm. MicroPET imaging of 4T1 tumor-bearing mice showed a gradual accumulation of the NPs in the tumor over time. About 6.5% of injected dose were taken up in each gram of tumor tissue at 24 h after intravenous injection of 64Cu-labeled PEG-CuS NPs. For both photoacoustic imaging and therapeutic studies, nanosecond (ns)-pulsed laser was delivered with Q-switched Nd:YAG at a wavelength of 1064 nm. Unlike conventional photothermal ablation therapy mediated by continuous wave laser with which heat could spread to the surrounding normal tissue, interaction of CuS NPs with short pulsed laser deliver heat rapidly to the treatment volume keeping the thermal damage confined to the target tissues. Our data demonstrated that it is possible to use a single-compartment nanoplatform to achieve both photoacoustic tomography and highly selective tumor destruction at 1064 nm in small animals.
Matching functions between loudness and ten other continua1

Cross-modality matches have been made between loudness and ten other perceptual continua. The matching functions are all power functions. When the exponent values of the matching functions are divided by the exponent values previously determined for the various continua, the quotients predict values for the loudness exponent. A tentative consensus suggests that the loudness exponent may be about 0.64.
A better estimate of the internal consistency reliability of frontal EEG asymmetry scores

Frontal alpha asymmetry is typically computed using alpha power averaged across many overlapping epochs. Previous reports have estimated the internal consistency reliability of asymmetry by dividing resting EEG sessions into segments of equal duration (e.g., 1 min) and treating asymmetry scores for each segment as "items" to estimate internal consistency reliability using Cronbach's alpha. Cronbach's alpha partly depends on the number of items, such that this approach may underestimate reliability by using less than the number of distinct items available. Reliability estimates for resting EEG data in the present study (204 subjects, 8 sessions) were obtained using mean split-half correlations with epoch alpha power as treated as separate items. Estimates at all scalp sites and reference schemes approached .90 with as few as 100 epochs, suggesting the internal consistency of frontal asymmetry is greater than that previously reported.
Path-a-Way: A Strategy for Network Analysis of Microarray Data

Microarray technology allows for high throughput gene expression studies. However, because of the large amounts of data produced, additional work is required to put the data into biological context. An emerging approach to provide this context is pathway and network analysis. The objective of this work was to design and implement such pathway analysis strategies. Our strategy identifies enriched biological pathways when given a list of genes found to be differentially expressed in a microarray experiment. After identification of these pathways,, our strategy generates scores to quantify how significant and functional the pathways are. These scores include statistical significance and unique graph theory scores such as pathway port connectedness, adjacency ratio, and completeness. Enzyme-centric scores are also generated to quantify the importance of each enzyme- coding gene in the pathway it participates in. Pathways in un-annotated organisms are inferred based on homology and several methods of visualizing the pathways are also provided. This approach can also be extended to proteomic data, or comparative genomic data to assess the relevance of a pathway or network in an organism or group of organisms.
Opportunity, Willingness, and the Diffusion of War

Using borders and alliances as indicators of opportunity and willingness, respectively, we test the relationship between these and the diffusion of war during the 1816–1965 period. The impact of borders and alliances, individually and in combination, on the growth of ongoing war through “infectious” diffusion is shown through the comparison of baseline cases to cases where states at peace were exposed to various “treatments” comprised of warring border nations or warring alliance partners. The findings indicate that the probability of war diffusion is substantially increased as opportunities and willingness increase, particularly when such geographic and political factors are combined. The applicability of the opportunity and willingness framework to the study of war and diffusion is expanded and confirmed.
Effect of ligands on the optical rotatory dispersion of hemoglobin. I. Ferrihemoglobin cyanide, ferrihemoglobin azide, ferrihemoglobin hydroxide, and carbonmonoxyhemoglobin†‡

The optical rotatory dispersion curves of ferrihemoglobin at pH 6 and 9.5, ferrihemoglobin cyanide, ferrihemoglobin azide, and carbon monoxyhemoglobin have been measured over the wavelength interval 500–190 mμ. Helix contents, based on the measured rotations at 233 and 200 mμ are estimated for the ferrihemoglobin derivatives on the basis of comparison with the rotations of the helical poly-α,L-glutamic acid. For the latter, a mean value of −14,200° is found for [m′]233 and 65,000° for [m′]200. Within experimental error, all the ferrihemoglobins examined have the same helix content, the value of which is 65% based on rotations at 233 mμ and 72% based on rotations at 200 mμ. Thus, the addition of ligands to ferrihemoglobin which enormously stabilize the molecule to acid denaturation and involve heme–heme interaction has no effect on the number of amino acid residues which are in α-helical segments. Change of pH from 6.8 to 5.0, through which interval the molecular weight decreases to that of the dimer, also leaves the helix content essentially unchanged, although at pH 5 heme–heme interaction in the binding of cyanide ion to ferrihemoglobin is absent. In addition to the Soret band Cotton effect observed for all the hemoglobin derivatives examined, there is at least one (and possibly two) other heme Cotton effects at wavelengths intermediate tot he Soret Cotton effect near 400 mμ and the n-π* peptide bond transition near 225 mμ. The Soret band Cotton effect is different in magnitude in all the derivatives examined, the most notable difference being in the pronounced intensification of this Cotton effect in CO-hemoglobin relative to the ferrihemoglobin derivatives. Similar differences have been observed by others in different myoglobin derivatives as well. While the changes are not so large as observed with hemoglobin, this indicates that these altered magnitudes are not directly related to the specific details of heme environment which give rise to differences in affinity for oxygen in the two proteins and result in a Bohr effect in hemoglobin but not in myoglogin.
Network virtualization and software defined networking for cloud computing: a survey

Network virtualization is the key to the current and future success of cloud computing. In this article, we explain key reasons for virtualization and briefly explain several of the networking technologies that have been developed recently or are being developed in various standards bodies. In particular, we explain software defined networking, which is the key to network programmability. We also illustrate SDN?s applicability with our own research on OpenADN - application delivery in a multi-cloud environment.
Scaling of speed and endurance in garter snakes: a comparison of cross‐sectional and longitudinal allometries

This study used cross-sectional (one observation per each of several individuals of diflerent size) and longitudinal (more than one observation through time per individual) methods to determine the effects of size on speed and endurance of Ti~amnophb~ .~ir/olisj/chi. The cross-sectional sample consisted of 497 snakes from a single population. Log of mean burst speed in this group measured over 50 cm (V50) was a quadratic function of log of snout-vent length (SVL); the slope of this polynomial ranged from about 1.6 to -0.3 for the smallest to the largest snakes (maximal V50 at 50.6 cm SVL). Longitudinal measurements of log V5O also were quadratically related to log SVL, but the slopes varied depending on year in which performance was measured. Cross-sectional allometry revealed that the slope of the regression relating log(endurance) to log(SVL) was about 2.3, and longitudinal estimates of this quantity ranged from 0.5 to 3.2, depending on the year. Sex did not affect burst speed, but females had significantly less endurance than males of equal SVL, and pregnancy had a significant detrimental effect on both speed and endurance. Regressions with SVL as the independent variable were used to generate size-corrected (residual) values of speed, endurance and mass, and each of these residuals had significant repeatability. For example, during 1986 the short-term repeatabilities (Pearson's r) of speed and endurance residuals were 0.65 (P<0.001) and 0.57 (P<0.001). From 1986 to 1987, year-to-year repeatabilities of speed, endurance and mass residuals were 0.25 (P=0.001), 0.22 (P=0.005) and 0.47 (P<0@01), respectively. Analysis of these three respective residual values of 264 neonatal snakes from 34 litters revealed highly significant percent variance components attributable to litter of 14%, 34% and 36%, yielding respective heritabilities of O.28,0.68 and 0.72. Speed and endurance residuals had a low but significant positive correlation (r=0,26. n=497), due apparently to snakes with poor performance: high speed is not linked with high endurance. A squared value of the mass residual had a significant negative correlation with both speed residual (r= -0.105, n=497) and endurance residual (-0.24), suggesting that snakes deviating from a mean value of mass relative to length havea slight decrement in locomotor performance. Longitudinal estimates of the scaling of mass with length revealed significant variation associated with different ages of snakes and different years of the study that could not be obtained from cross-sectional data.
Notes on Radiation from Horizontal Antennas

Experiments on the radiation from various types of low horizontal antennas are described. A 2-kilowatt, 500-cycle quenched spark set is used at a wave length of 800 meters. The influence of the ground is investigated. Directional radiation is found, and also an apparent non-reciprocity between directions of non-radiation and those of non-reception.
A Processive Carbohydrate Polymerase That Mediates Bifunctional Catalysis Using a Single Active Site

Even in the absence of a template, glycosyltransferases can catalyze the synthesis of carbohydrate polymers of specific sequence. The paradigm has been that one enzyme catalyzes the formation of one type of glycosidic linkage, yet certain glycosyltransferases generate polysaccharide sequences composed of two distinct linkage types. In principle, bifunctional glycosyltransferases can possess separate active sites for each catalytic activity or one active site with dual activities. We encountered the fundamental question of one or two distinct active sites in our investigation of the galactosyltransferase GlfT2. GlfT2 catalyzes the formation of mycobacterial galactan, a critical cell-wall polymer composed of galactofuranose residues connected with alternating, regioisomeric linkages. We found that GlfT2 mediates galactan polymerization using only one active site that manifests dual regioselectivity. Structural modeling of the bifunctional glycosyltransferases hyaluronan synthase and cellulose synthase suggests that these enzymes also generate multiple glycosidic linkages using a single active site. These results highlight the versatility of glycosyltransferases for generating polysaccharides of specific sequence. We postulate that a hallmark of processive elongation of a carbohydrate polymer by a bifunctional enzyme is that one active site can give rise to two separate types of glycosidic bonds.
Purchasing and Supplier Involvement: Issues and Insights Regarding New Product Success

SUMMARY This research examines the effects of purchasing and supplier involvement on new product success. Two hundred fifty-two senior purchasing managers completed a mail questionnaire that addressed a wide range of issues regarding the effects of purchasing and supplier involvement, the management of supplier involvement, the organization's strategic orientation, and the organization's competitive environment on new product success. The results indicate that the organization's strategic orientation and competitive environment, purchasing involvement, and supplier involvement affect new product success. The appropriate level, timing, and frequency of supplier involvement was found to vary with the situation. The results also provide insight into the role of purchasing in new product development and the effective management of supplier involvement in new product development.
Concepts of Fever

cal thermometry, few physicians could identify the source or explain the pertinacity of the belief that 98.6°F (37.0°C) has special meaning vis-a `-vis normal body temperature. Fewer still could cite the origin of the thermometer or trace the evolution of modern concepts of clinical thermometry. Although many would have some knowledge of the fundamentals of thermoregulation and the role played by exogenous and endogenous pyrogens in the induction of fever, few would have more than a superficial knowledge of the broad biological activities of pyrogenic cytokines or know of the existence of an equally complex and important system of endogenous cryogens. A distinct minority would appreciate the obvious paradoxes inherent in an enlarging body of data concerned with the question of fever’s adaptive value. The present review considers many of these issues in the light of current data.
Skin tissue cholesterol assay correlates with presence of coronary calcium

Abstract Background: Keratinocytes maintain cholesterol homoeostasis using LDL and HDL-scavenger receptor pathways implicated in atherosclerosis. We tested whether skin tissue cholesterol (SkTC) is associated with subclinical atherosclerosis, assessed using carotid intima-medial thickness (IMT) and coronary artery calcification (CAC). Methods: Two hundred and twenty two subjects were recruited from the Baltimore site of the Multi-Ethnic Study of Atherosclerosis (MESA). Baseline MESA examination included fasting blood collection, IMT measurement by B-mode ultrasound and CAC determination by helical CT. SkTC was measured using the Cholesterol 1, 2, 3 kit (IMI Inc., Canada). Results: SkTC was significantly higher if CAC was present in Caucasians ( p =0.04) but not African–Americans. SkTC was not significantly correlated with IMT in either group. Using multiple logistic regression adjusting for age, sex and serum lipids, a 1-standard deviation higher SkTC was associated with 187% higher odds of the presence of CAC in Caucasians ( p Conclusions: SkTC was associated with the presence of CAC independently of serum lipids/lipoproteins in Caucasians but not African–Americans. SkTC may provide a useful indicator of subclinical atherosclerosis in Caucasians.
Predicting Safety Related Attitudes in the Workplace: The Influence of Moral Maturity and Emotional Intelligence

Safety in the workplace has received an increasing amount of attention for over 50 years. Approaches to improving safety have focused primarily on extrinsic drivers such as engineering safer work environments, training, and policies. These efforts have reduced injuries and reportable incidents. Yet, progress toward industry’s stated goal of zero incidents has stalled. This paper explores an approach to creating a safer work environment using intrinsic drivers instead of compliance oriented behaviors. The Theory of Planned Behavior (Ajzen, 1985) is employed to show that moral maturity and emotional intelligence can act as intrinsic drivers, positively influencing safety attitudes and behavior.
“America’s Glory Road” … On Ice: Permafrost and the Development of the Alcan Highway, 1942–1943

The 2,250 km Alaska-Canada (“Alcan”) Highway was developed through nearly uncharted wilderness over a period of only seven months in 1942. The road was one of the largest engineering projects undertaken in North America to that time. The project was motivated by the need to transport personnel and materiel to and from Alaska Territory via a secure overland route and to service airfields in the new Northwest Staging Route, by which aircraft were supplied to the Soviet Union under the terms of the Lend-Lease Act of 1941. The largest single obstacle to the construction and efficient operation of the initial Alcan “pioneer road” was ice-rich permafrost. Despite some prior experience with permafrost engineering in North America and repeated warnings by Arctic experts about the use of mid-latitude engineering techniques in permafrost regions, the U.S. Army initially adopted conventional construction techniques, with disastrous consequences. To remediate the situation, a permafrost engineering manual was commissioned and prepared by Dr. Siemon W. Muller, a Stanford University geology professor of Russian extraction. The manual, issued in classified form in 1943, was used to guide the reconstruction and realignment of permafrost-affected sections of the road. Republished in revised format by a private printer in 1947, Muller’s book was used widely in subsequent engineering projects in Alaska and northern Canada. Today, the renamed Alaska Highway is an all-season, hard-surfaced roadway providing access to Alaska and intermediate Canadian settlements.
KINEMATICS OF THE TONGUE-BITE APPARATUS IN OSTEOGLOSSOMORPH FISHES

Summary Osteoglossomorph fishes are characterized by the possession of three sets of jaws used during the capture, maceration and swallowing of prey. One of these jaw systems is a remarkable tongue-bite apparatus used during the intraoral' crushing and shredding of prey. Kinematics of the tongue-bite apparatus were quantified, using 200 frames s" 1 video and film records of feeding in three genera of osteoglossomorph fishes {Osteoglossum, Pantodon and Notopterus) to examine the biomechanics and function of this mechanical system. Two distinct chewing behaviors associated with the tongue-bite apparatus were identified: raking and open-mouth chewing. In all three species, raking behavior involves holding the prey firmly in the mandibular jaws while the teeth of the tongue-bite apparatus are moved into the prey. However, other aspects of raking behavior are significantly different among the species: for example, only Notopterus uses extensive posterior movement of the pectoral girdle to pull basihyal teeth through the prey. In both Osteoglossum and Pantodon there is little motion of the pectoral girdle, and neurocranial elevation plays the major mechanical role in prey reduction, but there are also kinematic differences between Osteoglossum and Pantodon during raking. The kinematics of open-mouth chewing behavior are also significantly different among the three species. Thus, osteoglossomorph fishes share a similar morphology of the tongue-bite apparatus derived from a common ancestor, but have acquired independent kinematic specializations associated with its use.
The Role of Food Production in Incipient Warfare in Protohistoric Timor Leste

This chapter explores causal linking mechanisms between environmental changes and the beginnings of group conflict as represented by fortification building. It focuses on issues of food production in mixed agricultural/gathering economies and their role in mediating group conflict. The primary case study used to explore these links is the fortified settlements of Timor Leste, which first appear about 1100 C.E. At this time, Timorese engaged in a diverse array of subsistence strategies including dry and irrigated agriculture, domestic animal husbandry, fishing, hunting, and foraging for wild plant and animal resources and extensive trade that likely included food products. Although the island has documented human occupation dating as far back as 45 kya, fortifications appear on the landscape quite suddenly and extensively, although not in all areas simultaneously. This chapter reviews previous explanatory models and suggests avenues for future research on the links between changes in environment, food production, and warfare, with a focus on strategies to deal with underlying tensions about environmental determinism, chronological uncertainty, and disjunctions between textual and archaeological evidence.
In vitro and in vivo antiviral (RNA) evaluation of orotidine 5'-monophosphate decarboxylase inhibitors and analogues including 6-azauridine-5'-(ethyl methoxyalaninyl) phosphate (a 5'-monophosphate prodrug)

Summary A series of 29 pyrimidines comprising analogues of 6­ azauridine (e.g. 2- and 4-thio-6-azauridine), 6-substituted uridines (including several known inhibitors of orotidine 5'­ monophosphate decarboxylase, ODCase, e.g. pyrazofu­ rin), and 6-azauridine-5'-(ethyl methoxyalaninyl) phos­ phate (a potential prodrug of 6-AU-5'-MP) were synthesized and evaluated in vitro and in vivo against five RNA viruses: Japanese encephalitis (JE), yellow fever (YF), sandfly fever (SF), Punta Toro (PT) and Venezuelan equine encephalomyelitis (VEE) viruses. 2-Thio-6-azauri­ dine demonstrated the best in vitro activity against all five viruses. However, in vivo activity was not observed in JE-, PT- and VEE-infected mice. The phosphate prodrug of 6­ azauridine was significantly more effective than the par­ ent compound in the PT virus mouse model. Optimum in vivo dose/route/schedule was determined for pyrazofurin in PT-virus-infected mice.
Introduction: teaching energy geographies

In his introduction to the 2011 special issue on energy of the Annals of the Association of American Geographers, Karl Zimmerer argues that “Geography is central to understanding and addressing the...
Wintering at Little Island Rock: A Fur Trade Site on Grand Island

AbstractResearch conducted by Hiawatha National Forest personnel in 2000–2002 investigated the well-preserved archaeological remains of a circa 1820s fur trader’s wintering post located on Grand Island, near the south shore of Lake Superior. The most likely occupant of this post was Henry A. Levake, a trader from Sault Sainte Marie (St. Mary’s Falls) who was accompanied by his Native American wife. Both archaeological and historical information show that the Little Island Rock Post is an example of a specialized cold-climate adaptation developed in the boreal forests of North America and in the northern portion of the temperate forests to the south. Key elements of this adaptation include: location near a late fall or winter fishery, use of large amounts of clay for chimney construction, and the presence of ample storage facilities, especially pits. Features associated with this adaptation at the Little Island Rock Post also reflect the multiethnic occupational subculture of the fur trade. This site fills...
Gold thiomalate-induced weight gain in guinea pigs.

SummaryRepeated injections of gold sodium thiomalate in guinea pigs resulted in significant weight gain. Retroperitoneal fat deposits and extractable omental fat were increased in treated animals. Neutron activation analysis and autoradiography localized gold within brain macrophages of treated animals. However, specific concentration of gold in hypothalamic nuclei and tissue destruction were not observed. The absence of lesions and the failure to demonstrate hyper-phagia suggest that gold thiomalate induces a metabolic obesity rather than a regulatory obesity in guinea pigs.
The Electric Quadrupole Moment of In^(115)

Measurements of the lines λ7852 (5s6p^1P→5s6s^1S) are λ8241 (5s6p^1P→5s5d^1D) of In II show deviations from interval rule. These deviations are satisfactorily accounted for by the presence of a nuclear electric quadrupole moment which from the first of the lines is found to be Q=0.82×10^(−24) cm^2. No trace of lines due to In^(113) was found.
Effects of Obstructive Sleep Apnea and Obesity on Cardiac Remodeling: The Wisconsin Sleep Cohort Study.

STUDY OBJECTIVES To characterize the prospective associations of obstructive sleep apnea (OSA) with future echocardiographic measures of adverse cardiac remodeling. METHODS This was a prospective long-term observational study. Participants had overnight polysomnography followed by transthoracic echocardiography a mean (standard deviation) of 18.0 (3.7) y later. OSA was characterized by the apnea-hypopnea index (AHI, events/hour). Echocardiography was used to assess left ventricular (LV) systolic and diastolic function and mass, left atrial volume and pressure, cardiac output, systemic vascular resistance, and right ventricular (RV) systolic function, size, and hemodynamics. Multivariate regression models estimated associations between log10(AHI+1) and future echocardiographic findings. A secondary analysis looked at oxygen desaturation indices and future echocardiographic findings. RESULTS At entry, the 601 participants were mean (standard deviation) 47 (8) y old (47% female). After adjustment for age, sex, and body mass index, baseline log10(AHI+1) was associated significantly with future reduced LV ejection fraction and tricuspid annular plane systolic excursion (TAPSE) ≤ 15 mm. After further adjustment for cardiovascular risk factors, participants with higher baseline log10(AHI+1) had lower future LV ejection fraction (β = -1.35 [standard error = 0.6]/log10(AHI+1), P = 0.03) and higher odds of TAPSE ≤ 15 mm (odds ratio = 6.3/log10(AHI+1), 95% confidence interval = 1.3-30.5, P = 0.02). SaO2 desaturation indices were associated independently with LV mass, LV wall thickness, and RV area (all P < 0.03). CONCLUSIONS OSA is associated independently with decreasing LV systolic function and with reduced RV function. Echocardiographic measures of adverse cardiac remodeling are strongly associated with OSA but are confounded by obesity. Hypoxia may be a stimulus for hypertrophy in individuals with OSA.
An Improved WebGIS Application in Emergency Command System

Power emergency command system plays an important role in serious accident,equipment damage,power supply crisis during power production associated with natural disasters,significant emergency and public security events.It provides technical support to decision makers,and has important significance for the safe and reliable operation of power system.Based on the characteristics and demands of the emergency command system of China Southern Power Grid,this paper introduces an efficient data processing method at server-side based on WebGIS in this system,and discusses client architecture and the real-time communication at both client and server-side.
Behavioral Pediatrics and the Practicing Pediatrician

Descriptions of the “new pediatrics” and questions about its practice began to appear in the 1950’s. The author describes how “behavioral pediatrics” can be and is being practiced in a private office in the 1970’s. Answering questions about the time required, the personnel needed, and fees to be charged, a model is proposed.
ATAM assistant: a semi-automated tool for the architecture tradeoff analysis method

The Architecture Tradeoff Analysis Method (ATAM) pioneered by the Software Engineering Institute at Carnegie Mellon University has shown great promise in ensuring that a software system's most important non functional requirements can be realized given the system's architecture. ATAM has been applied in several published case studies to evaluate the architecture of existing software systems and create architectures to meet critical non-functional requirements. This paper presents the ATAM Assistant which semi-automates several tasks involved in this process. ATAM Assistant's goal is to be a single application to manage, visualize, and report on all of the process artifacts generated during this process.
Pax5 Activates Oncogenic Transcription Factors of the Ets Family by Repressing the mir-15a/16-1 microRNA Cluster.

Abstract We have recently demonstrated that Pax5 promotes B-lymphomagenesis by upregulating key components of B-cell receptor signaling [Cozma et al, J Clin Inv, 117 (8), 2007]. Gene regulation by Pax5 often involves complex formation with other oncogenic transcription factors of the Ets family, namely Myb and Ets1. We determined that expression of these proteins themselves depends on the presence of Pax5, as seen in human diffuse large B-cell lymphomas with Pax5 knockdown and murine lymphomas with epigenetic silencing of Pax5 [Yu et al, Blood , 101:1950–1955, 2003; Johnson et al, Nat Immunol , 5:853–861, 2004]. Upon reconstitution with the Pax5 gene, Myb and Ets1 levels increase sharply. This occurs with little increase in steady-state mRNA levels, suggesting post-transcriptional regulation, possibly by microRNAs. To test this hypothesis, we compared miRNA profiles of Pax5-deficieint and sufficient cells and discovered that several miRNAs are indeed repressed by Pax5. Among them is the miR-15a/16-1 cluster whose predicted targets include both Myb and Ets1. Consistent with this prediction, forced expression of miR-15a/16 brings down Myb and Ets1 protein levels. This is accompanied by impaired Pax5 function and overall suppression of B-lymphomagenesis. Thus, Ets family members (along with previously identified bcl-2) are key targets of the miR-15a/16 locus, a tumor suppressor in chronic lymphocytic leukemia. Download : Download high-res image (188KB) Download : Download full-size image Interplay between Pax5, Myb/Ets1, and miR-15a/16-1. (A) Upregulation of Myb and Ets 1 in tumors over-expressing Pax5ER fusion, as compared to control GFP-only neoplasms. (B) Down-regulation of Myb and Ets1 in Pax5 tumors engineered to over-express the miR-15a/16-1 cluster. All panels depict Western blotting.