cssi/SciSciGPT-SciSciNet huggingface dataset:
Gender differences in the responsiveness of the sex-dependent isoforms of hepatic P450 to the feminine plasma growth hormone profile.

Most of the constitutive hepatic P450 isoforms expressed in the rat exhibit dramatic gender differences. Whereas only male hepatocytes contain CYP2A2, 2C11, and 3A2, only female hepatocytes express CYP2C12 and 3- to 4-fold greater levels of CYP2C7. This sexually dimorphic expression of hepatic P450 isoforms is regulated by the gender-dependent secretory GH profiles, i.e. episodic in males and continuous in females. In the case of the feminine GH profile, the continuous presence of the hormone in the circulation completely suppresses male-specific CYP2A2, 2C11, and 3A2, while stimulating full expression of female-dependent CYP2A1, 2C7, 2C12, and non-P450 testosterone 5α-reductase (type 1). The gender-dependent expression of the P450s can be reversed by exposing male rats to the continuous feminine plasma GH profile and females to the episodic masculine GH profile. Under these conditions, females will now express the male-specific isoforms and suppress the female-dependent forms, whereas the opposite will o...
Synthetic biology as red herring.

Abstract It has become commonplace to say that with the advent of technologies like synthetic biology the line between artifacts and living organisms, policed by metaphysicians since antiquity, is beginning to blur. But that line began to blur 10,000 years ago when plants and animals were first domesticated; and has been thoroughly blurred at least since agriculture became the dominant human subsistence pattern many millennia ago. Synthetic biology is ultimately only a late and unexceptional offshoot of this prehistoric development. From this perspective, then, synthetic biology is a red herring, distracting us from more thorough philosophical consideration of the most truly revolutionary human practice—agriculture. In the first section of this paper I will make this case with regard to ontology, arguing that synthetic biology crosses no ontological lines that were not crossed already in the Neolithic. In the second section I will construct a parallel case with regard to cognition, arguing that synthetic biology as biological engineering represents no cognitive advance over what was required for domestication and the new agricultural subsistence pattern it grounds. In the final section I will make the case with regard to human existence, arguing that synthetic biology, even if wildly successful, is not in a position to cause significant existential change in what it is to be human over and above the massive existential change caused by the transition to agriculture. I conclude that a longer historical perspective casts new light on some important issues in philosophy of technology and environmental philosophy.
Tumor radioresponsiveness versus fractionation sensitivity

Since the introduction of mammalian cell survival curves, the parameters D0 and N have been used as quantitative measures of inherent radiation sensitivity, as was the shoulder width Dq. These parameters are more generally applicable at high doses. We propose to introduce a measure of tumor radioresponsitivity that is more applicable to the clinical treatment schedules that employ small fractional doses (1-2 Gy), the ratio alpha/E, derived from the linear quadratic model for cell inactivation as the intercept on the reciprocal-dose plot. For tumor-control experiments this ratio is the reciprocal of the TCD50 when radiation is given in very small fractions or at low dose rates (assuming negligible clonogen proliferation). The rationales for this choice are: alpha is a measure of the steepness of the initial linear segment of the dose-survival curve. Accordingly, at doses per fraction of 1-2 Gy the observed effect increases with alpha. E is by definition a positive measure of the clonogen kill required for a specified tumor response, e.g., E = -log (surviving fraction of clonogens at the 50% control level). Therefore it is also a measure of the number of clonogens present at the time of inception of treatment, which for a given dose is a prime determinant of the probability of tumor control. This measure of radioresponsitivity is to be distinguished from the ratio alpha/beta, which is a measure of fractionation sensitivity. A survey of the literature indicates that these do not correlate, except in highly hypoxic tumors (e.g., clamped); such tumors are characterized by low radioresponsitivity as well as low fractionation sensitivity (high alpha/beta ratio). There are at present only limited data for determination of this ratio, however, since reciprocal-dose analysis requires tumor control doses for several different sizes of dose per fraction.
Sequestering Atmospheric Carbon Dioxide

The abrupt climate change, attributed to increase in atmospheric concentration of CO 2 and other greenhouse gases, has necessitated identification of technological options to sequester CO 2 into other long-lived pools. Other viable pools for C sequestration include geologic, oceanic, and the terrestrial. There is also a potential to convert CO 2 into stable minerals. There are geoengineering techniques of CO 2 capture and storage into old oil wells to enhance oil recovery (EOR) and access coalbed methane (CBM), store in saline aquifers and sedimentary rocks, and combine it with basalt where it goes through chemical transformations. Geoengineering techniques have relatively high sink capacity and also high costs. Further, geoengineering techniques require measurement, monitoring, and verification (MMV) protocols. In contrast, C sequestration in terrestrial ecosystems (soil and biota) is based on the natural process of photosynthesis, and humification of biosolids applied to the soil. Terrestrial pools have...
Differential effects of novel protamine variants on myocyte contractile function with left ventricular failure.

Background. Protamine administration can cause left ventricular (LV) dysfunction, which may have clinical significance in the setting of congestive heart failure (CHF). Protamine variants have recently been constructed with heparin reversal capacity similar to protamine. The purpose of this study was to examine the potential differential effects of these protamine variants on isolated myocyte contractile function in normal myocytes and in myocytes after the development of CHF. Methods. Contractile function was measured by means of computer-aided videomicroscopy in myocytes from five normal pigs and five pigs with CHF induced by rapid pacing (240 beats/min for 3 weeks). Myocyte contractility was examined in the presence of 40 μg/ml native protamine or one of three protamine variants: (1) reduced charge (+18) and lysine substituted for arginine; (2) lysine-substituted variant with glutamic acid substituted for the initial proline; or (3) arginine-rich peptide with a terminal arginine-glycine-aspartic acid (RGD) amino acid sequence. Results. In the presence of native protamine, myocyte percent shortening fell from baseline in both the normal (2.86 ± 0.15 versus 4.58 ± 0.08, p < 0.05) and the CHF groups (1.01 ± 0.06 versus 2.07 ± 0.05, p < 0.05). With both of the lysine-substituted protamine variants, percent shortening fell from baseline in the normal group (3.42 ± 0.20 for arginine and 3.74 ± 0.20 for glutamic acid versus 4.58 ± 0.08, p < 0.05), and was unchanged in the CHF group (1.94 ± 0.13 versus 2.07 ± 0.05, p = 0.34 for arginine; and 1.96 ± 0.10 versus 2.07 ± 0.05, p = 0.31, for glutamic acid). However, with the arginine/RGD variant, percent shortening fell from baseline in both the normal (2.86 ± 0.23 versus 4.58 ± 0.08, p < 0.05) and the CHF groups (1.32 ± 0.10 versus 2.07 ± 0.05, p < 0.05). Conclusions. Specific changes in the primary and secondary structures of protamine had different effects on myocyte contractile function. Furthermore, the negative effects of ly sine-substituted protamine variants on myocyte contractility were less pronounced in both CHF and normal myocytes. Thus protamine variants may be of clinical use, particularly in the setting of preexisting LV dysfunction.
Fluorescent probes for the structure and function of metallothionein

Fluorescence methods have been instrumental in demonstrating that the structure of human metallothionein in vivo depends on the availability of metal ions and the redox environment. Differential chemical modifications of its cysteine thiols with fluorescent probes allowed determination of three states: metallothionein (zinc-bound thiolate), thionein (free thiols), and thionin (disulfides). Interrogation of its zinc-binding properties with fluorescent chelating agents revealed that the affinities for the seven zinc ions vary over four orders of magnitude. Attachment of fluorescent labels generated metallothionein FRET (fluorescence resonance energy transfer) sensors for investigating its structure and function in living cells.
Nerves of bicategories as stratified simplicial sets

Abstract In this paper, we aim to move towards a definition of weak n -category akin to Street’s definition of weak ω -category. This will be accomplished in dimension 1 directly and in dimension 2 by comparison with work of Duskin. In particular, we discuss the relationship between certain weak complicial sets and Duskin’s n -dimensional Postnikov complexes.
Identification of oxidized derivatives of neuroketals

Oxidative stress and protein aggregation have been implicated in the pathogenesis of neurodegenerative diseases. The formation of neuroprostanes, isoprostane-like compounds formed from oxidation of docosahexaenoic acid, which is uniquely enriched in the brain, is increased in Alzheimer's disease. We recently identified the formation of a new class of highly reactive gamma-keto aldehydes, neuroketals, in vivo as products of the neuroprostane pathway. Neuroketals adduct to lysine residues of proteins with remarkable rapidity and induce cross-linking. Because neuroketals have either a 1,4-pentadiene or 1,4,7-octatriene side chain structure, we hypothesized that they could undergo further oxidation to form neuroketals with an additional hydroxyl group. Oxidation of docosahexaenoic acid in vitro yielded a series of compounds that were confirmed to be oxidized neuroketals by mass spectrometric analyses. Analysis of oxidized neuroketal adducts during oxidation of docosahexaenoic acid in the presence of lysine revealed the formation of oxidized Schiff base and hydroxylactam adducts. Oxidized hydroxylactam neuroketal-lysyl protein adducts, analyzed after digestion of proteins to individual amino acids, were not detected in nonoxidized rat brain synaptosomes but were readily detected following oxidation of synaptosomes. These studies indicate that neuroketals can undergo further oxidation, which in turn suggests that measurement of only unoxidized neuroketal adducts likely underestimates the amount of neuroketal adducts present in the brain in disorders of oxidant stress.
The distal left Malone antegrade continence enema--is it better?

Purpose: The Malone antegrade continence enema is used for refractory fecal dysfunction in the pediatric neuropathic population. While various locations along the colon have been described, the optimal site for achieving efficient enemas remains unknown. We reviewed our experience with the Malone antegrade continence enema procedure and investigated functional outcomes and complications associated with proximal and distal locations.Materials and Methods: We performed an institutional review board approved, retrospective chart review of 109 consecutive MACE procedures done by a single surgeon from 2000 to 2012. Preoperative patient characteristics, intraoperative techniques and postoperative outcomes were reviewed and statistical analysis was performed.Results: Included in analysis were 90 patients treated with a total of 109 MACE procedures. Average age at operation was 13.8 years. Myelomeningocele was the most common diagnosis. Most patients underwent simultaneous urinary reconstruction. Stomal complicat...
t-designs on hypergraphs

A t-design T=(X, B), denoted by (@l; t, k, v), is a system B of subsets of size k from a v-set X, such that each t-subset of X is contained in exactly @l elements of B. A hypergraph H=(Y, E) is a finite set Y where E=(E"i: [email protected]) is a family of subsets (which we assume here are distinct) of Y such that E"i O, [email protected], and @?E"i=Y. Let G be an automorphism group of H=(Y, E) where O^l"i is the ith orbit of l-subsets of E. Let A(G; H; t, k)= (a"i"j) be an m by n matrix, where a"i"j is the number of copies of O^t"i that occur in the system of all t-subsets of all elements of O^k"j. Then there is a t-design T=(X, B) with X=E, with parameters (@l; t, k, v), and with G an automorphism groupof T iff there is an m by s submatrix M of A(G; H; t, k) where M has uniform row sums @l. The calculus for applying this theorem is illustrated and numerous t-designs for 10=
Isolation and properties of thiogalactoside transacetylase-negative mutants of Escherichia coli

Abstract Mutants which lacked thiogalactoside transacetylase were isolated from ML and K12Escherichia coli strains. When the parental cells were incubated overnight on amino acid containing agar plates in the presence of thio[14C]methyl-β- d -galactopyranoside ([14C]TMG), they converted a considerable fraction of the external thiogalactoside to the acetyl derivative which diffused out of the cell into the incubation medium. The mutants, on the other hand, did not reduce the external TMG concentration by metabolism, and were consequently able to accumulate more radioactivity within the cells. 14C content of each clone was determined by preparing an imprint of the clones on filter paper which, after drying, was exposed to photographic film. Several properties of these acetylase-negative mutants were studied.
Effects of elevated co2 and herbivore damage on litter quality in a scrub oak ecosystem.

Atmospheric CO2 concentrations have increased dramatically over the last century and continuing increases are expected to have significant, though currently unpredictable, effects on ecosystems. One important process that may be affected by elevated CO2 is leaf litter decomposition. We investigated the interactions among atmospheric CO2, herbivory, and litter quality within a scrub oak community at the Kennedy Space Center, Florida. Leaf litter chemistry in 16 plots of open-top chambers was followed for 3 years; eight were exposed to ambient levels of CO2, and eight were exposed to elevated levels of CO2 (ambient + 350 ppmV). We focused on three dominant oak species, Quercus geminata, Quercus myrtifolia, and Quercus chapmanii. Condensed tannin concentrations in oak leaf litter were higher under elevated CO2. Litter chemistry differed among all plant species except for condensed tannins. Phenolic concentrations were lower, whereas lignin concentrations and lignin/nitrogen ratios were higher in herbivore-damaged litter independent of CO2 concentration. However, changes in litter chemistry from year to year were far larger than effects of CO2 or insect damage, suggesting that these may have only minor effects on litter decomposition.
Characterization of a High-Gain Harmonic-Generation Free-Electron Laser at Saturation

We report on an experimental investigation characterizing the output of a high-gain harmonic-generation (HGHG) free-electron laser (FEL) at saturation. A seed CO2 laser at a wavelength of 10.6 microm was used to generate amplified FEL output at 5.3 microm. Measurement of the frequency spectrum, pulse duration, and correlation length of the 5.3 microm output verified that the light is longitudinally coherent. Investigation of the electron energy distribution and output harmonic energies provides evidence for saturated HGHG FEL operation.
Frederic Wood-Jones: The ideal lesion produced by hanging

Abstract The ideal lesion produced by judicial hanging, as described by Frederic Wood-Jones in 1913, is traumatic spondylolisthesis of the axis with bilateral fracture through the neural arch and dislocation of the second cervical vertebra on the third. A lesion with identical configuration has since been extensively described, generally in association with vehicular trauma. The mechanism of injury of this “hangman's fracture” is thought usually to involve hyperextension and axial loading. Absence of permanent neurologic deficit and union with conservative management are the rule. The plain lateral radiograph of the cervical spine is usually the basis for diagnosis. Although computerized tomography may reveal subtleties not apparent on the plain radiograph, it generally adds little to management.
Thinking Technology, Thinking Nature∗

The notion that technology is a mere tool at our disposal has become commonplace over the past one hundred years. According to this view technical devices can be explained as means that are used fo...
An efficient algorithm for the removal of impulse noise from corrupted images

Abstract In this letter, we propose an efficient algorithm, which can successfully remove impulse noise from corrupted images while preserving image details. It is efficient, and requires no previous training. The algorithm consists of two steps: impulse noise detection and impulse noise cancellation. Extensive experimental results show that the proposed approach significantly outperforms many other well-known techniques for image noise removal.
The distribution and ecology of Spiniferomonas (Chrysophyceae) in Connecticut (USA)

Siver, P. A. 1988. The distribution and ecology of Spiniferomonas (Chrysophyceae) in Connecticut (USA). - Nord. J. Bot. 8: 205–212. Copenhagen. ISSN 0107–055X. The genus Spiniferomonas was found to be a common member of the phytoplankton flora in Connecticut lakes, present in over thirty-seven percent of the 113 samples collected during 1984. Thirteen of the 15 known freshwater Spiniferomonas species were found including S. crucigera, recorded for the first time from North America. Six species were new records for the United States. S. trioralis, S. bilacunosa and S. bourrellyi were the most common taxa. Ecological preferences of some species are presented. This study represents the first major survey of the genus in the United States.
Tyrosine phosphorylation of extracellular signal-regulated protein kinase 4 in response to growth factors.

: Extracellular signal-regulated protein kinases (ERKs) are members of the mitogen-activated protein kinase family that are rapidly phosphorylated and activated in response to various extracellular stimuli, including growth factors. Of these, the ERK1 and ERK2 forms are by far the most abundant and the most studied. Much less is known about other ERK forms, including one previously designated ERK4 on the basis of its cross-reactivity with ERK1 and ERK2. We report here that ERK4 in rat PC12 pheochromocytoma cells can be immunoprecipitated by anti-ERK antiserum R2 and have used this reagent to characterize this species further. We find that ERK4 rapidly becomes tyrosine-phosphorylated in response to nerve growth factor (NGF) and epidermal growth factor (EGF) and, to a lesser degree, in response to insulin and a permeant cyclic AMP analogue. As in the case of ERK1 and ERK2, tyrosine phosphorylation of ERK4 occurs by a ras-dependent pathway in response to NGF and EGF and shows prolonged kinetics for NGF but not EGF treatment. Recognition by multiple antisera directed against various domains of ERK1 supports classification of ERK4 within the ERK family; however, two-dimensional gel analysis clearly distinguishes ERK4 from isoforms of ERK1. These findings thus reveal an additional member of the ERK family that is responsive to growth factors and that could play a distinct role in intracellular signaling.
Automating judgmental decisions using neural networks: a model for processing business loan applications

This paper presents a neural network model that simulates a business loan officer. The network is trained by showing financial ratios, past credit ratings, and loan records of a mixed sample of defaulted and non-defaulted companies. Once it is trained, it recommends to grant or deny a loan. The model uses human judgment of an expert as well as mathematical analysis of financial ratios. It includes into consideration the relative importance of different inputs, and the degree of belief in human judgments. An approach is shown, which allows an “explanation” for the decisions made. The results show that a neural network can be a valuable tool in simulating human decision-making.
Early Experience with Percutaneous Lateral Discectomy

Twenty-one patients are reported who underwent percutaneous lumbar discectomy for a herniated disc and sciatica. The criteria for inclusion in this series included: (1) a protruding disc in the lumbar area causing neural compression; (2) persistent sciatica; (3) failure of conservative treatment; (4) MRI, CT, or myelographic confirmation of the protrusion; (5) chronic low back pain with definite evidence of a protruding disc at the appropriate level. The only contraindication to the procedure is the presence of an extruded fragment. There were twelve males and nine females with an average age of 40. The operation is performed under local anesthesia and by the method of Kambin [3–6]. Twelve cases were at the L4–L5 level, eight were at the L5–S1 level, four were at the L3–L4 level, and one was at the L2–L3 level. Seventeen of 21 patients were relieved of their symptoms. One case was aborted due to inability to pass the cannula beneath arthritic facet joints. One complication occurred early while we were using general anesthetic. We injured an L 5 nerve root causing a permanent foot drop. Major possible complications include: (1) infection; (2) nerve root injury: (3) vascular injury. A success rate of 85% is reported.
A numerical investigation of different touchdown patterns of thermal-flying-height-control sliders

In this study we employ a numerical approach to explore the touchdown patterns of a thermal-flying-height-control (TFC) slider. Depending on the roughness of the head disk interface and thickness of the lubricant layer a TFC slider can experience different stages during touchdown. Three different touchdown patterns are shown. With a rougher interface profile the slider smoothly transfers from a flying stage to a sliding stage. With an intermediate smooth interface profile the slider experiences a flying-bouncing-sliding transition. With the smoothest interface the slider goes through a flying-bouncing-surfing-sliding transition. Different stages are characterized by different slider dynamics and slider-disk contact status. The different touchdown dynamic patterns shown here can result in a significant difference in the easiness of successful touchdown detection. The general approach proposed here may also be applied to investigate the effects of other important head disk interface factors, e.g., air bearing surface design, heater, suspension, etc. on the slider’s touchdown dynamic behaviors.
Moody's Analytical Overview of 25 Leading U.S. Cities—Revisited

Several attempts have been made to duplicate Moody's municipal bond ratings through the use of discriminant analysis. Based on cities and data published in Moody's Analytical Overview of 25 Leading U.S. Cities, Aronson and Marsden (A &M) report that they achieved 83% accuracy when classifying according to five bond rating groups and 95% accuracy when discriminating between cities with high and low bond ratings. They also indicate that the most important variable in this model is the percentage of a city's population that is black (PB). This article attempts to validate A&M's findings through the use of additional statistical techniques. By employing Lachenbruch's U-Method, it is found that the 83% and 95% classification accuracies reported fall to 25% and 70.8%. It is also found that by eliminating variables, the U-Method accuracy increases to 87.5% for the two-group model. The conditional deletion method supports A & M's findings concerning the relative importance of PB, and thejackknife technique indica...
Using Standardized Diagnostic Instruments to Classify Children with Autism in the Study to Explore Early Development

The Study to Explore Early Development (SEED) is a multi-site case–control study designed to explore the relationship between autism spectrum disorder (ASD) phenotypes and etiologies. The goals of this paper are to (1) describe the SEED algorithm that uses the Autism Diagnostic Interview-Revised (ADI-R) and Autism Diagnostic Observation Schedule (ADOS) to classify children with ASD, (2) examine psychometric properties of different ASD classification methods, including the SEED method that incorporates rules for resolving ADI-R and ADOS discordance, and (3) determine whether restricted interests and repetitive behaviors were noted for children who had instrument discordance resolved using ADI-R social and communication scores. Results support the utility of SEED criteria when well-defined groups of children are an important clinical or research outcome.
Energetic and structural aspects of ethidium cation intercalation into DNA minihelices

The enthalpy ΔH for the intercalation of the ethidium cation (EC) into DNA minihelices can be decomposed into (1) an energy of conformational adjustment (i.e., the energy of minihelix extension and unwinding from the B-form to the intercalated form) and (2) EC minihelix intermolecular interactions. In the present study, we have focused our attention mainly on a decomposition of the energetic factors of the EC minihelix intermolecular interactions, while the essential features of the energy of conformational adjustment have been discussed in detail elsewhere by us. The structural features of the various resulting energy-minimized EC-intercalated complexes are compared with each other and the initial x-ray model structure. ΔH is estimated to be in the range of −12.3 to −24.0 kcal/mol. This theoretical estimate is qualitatively and quantitatively in agreement with a variety of available experimental data. The energy of conformational adjustment is an energetically unfavorable step, while the energetically favorable contribution of the EC minihelix intermolecular interactions is responsible for the overall favorable nature of the intercalation process involving the EC. On the other hand, the observed preference for intercalation into Pyr(3′–5′)Pur DNA sequences over their isomeric Pur(3′–5′)Pyr sequences is controlled by the energy of conformational adjustment and not by the EC minihelix intermolecular interaction contribution. No base-composition effect is expected at EC concentrations normally found at cellular conditions. Moreover, the structural features of the various EC-intercalated complexes are very similar regardless of minihelix base sequence or composition. These results compare favorably with available evidence. The nature of biologically preferred sites of EC binding with the minihelices is discussed.
Can host ecology and kin selection predict parasite virulence

Parasite virulence, or the damage a parasite does to its host, is measured in terms of both host costs (reductions in host growth, reproduction and survival) and parasite benefits (increased transmission and parasite numbers) in the literature. Much work has shown that ecological and genetic factors can be strong selective forces in virulence evolution. This review uses kin selection theory to explore how variations in host ecological parameters impact the genetic relatedness of parasite populations and thus virulence. We provide a broad overview of virulence and population genetics studies and then draw connections to existing knowledge about natural parasite populations. The impact of host movement (transporting parasites) and host resistance (filtering parasites) on the genetic structure and virulence of parasite populations is explored, and empirical studies of these factors using Plasmodium and trematode systems are proposed.
Natural resonance theory: III. Chemical applications

We describe quantitative numerical applications of the natural resonance theory (NRT) to a variety of chemical bonding types, in order to demonstrate the generality and practicality of the method for a wide range of chemical systems. Illustrative applications are presented for (1) benzene and polycyclic aromatics; (2) CO2, formate, and related acyclic species; (3) ionic and polar compounds; (4) coordinate covalent compounds and complexes; (5) hypervalent and electron-deficient species; (6) noncovalent H-bonded complex; and (7) a model Diels-Alder chemical reaction surface. The examples exhibit the general harmony of NRT weightings with qualitative resonance-theoretic concepts and illustrate how these concepts can be extended to many new types of chemical phenomena at a quanitative ab initio level. © 1998 John Wiley & Sons, Inc. J Comput Chem 19: 628–646, 1998
Non-astigmatic children's contrast sensitivities differ from anisotropic patterns of adults

Abstract Monocular contrast thresholds were estimated for horizontal (H), vertical (V) and left and right diagonal 10c/deg sinusoidal gratings for non-astigmatic children (4:10–11:2 yr) and adults using yes-no signal detection (YN) methods. Some children were also tested with two-interval forced-choice (2IFC). Younger children were less likely to have the typical adult pattern of anisotropic sensitivity, favoring H and V, while 10–11 yr olds had more adult-like anisotropy. Within all age groups patterns of anisotropy varied considerably. Deviation of adults from the typical pattern may be related to small amounts of astigmatism in their untested eyes. 4- and 5-yr olds were confused by 2IFC. For children 6 yr and older, 2IFC and YN threshold estimates were equivalent, but 2IFC required less testing time.
PERK-dependent regulation of IAP translation during ER stress

Exposure of cells to endoplasmic reticulum (ER) stress leads to activation of phosphatidylinositol 3-kinase (PI3K)-Akt signaling pathway and transcriptional induction of the inhibitor of apoptosis family of proteins. One of the proximal effectors of the ER stress response, the PKR-like ER kinase (PERK), leads to cellular adaptation to stress by multiple mechanisms, including attenuation of protein synthesis and transcriptional induction of pro-survival genes. Although PERK activity leads to cellular adaptation to ER stress, we now demonstrate that PERK activity also inhibits the ER stress-induced apoptotic program through the induction of cellular inhibitor of apoptosis (cIAP1 and cIAP2) proteins. This induction of IAPs occurs through both transcriptional and translational responses that are PERK dependent. Reintroduction of cIAP1 or cIAP2 expression into PERK-/- murine embryonic fibroblasts during ER stress delays the early onset of ER stress-induced caspase activation and apoptosis observed in these cells. Furthermore, we demonstrate that the activation of the PI3K-Akt pathway by ER stress is dependent on PERK, suggesting additional ways in which PERK activity protects cells from ER stress-induced apoptosis.
Mesenchymal stem cells--a new approach to intestinal ischemia/reperfusion injury?

Mesenchymal stem cells (MSCs) possess many properties that may make them suitable as transplanted therapeutic agents for ischemia/reperfusion injury (I/R). These properties include but are not limited to paracrine signaling [1], immunomodulation of the recipient environment [2, 3], and possibly differentiation into the injured tissue [4]. Several studies have investigated the effects of MSCs with respect to I/R of the heart [5], brain [6] and kidney [7]. However, the role of MSCs has not been determined in the setting of intestinal I/R. In this issue, Jiang and colleagues studied this question in a rat model of I/R [8]. Using an established model, the superior mesenteric artery (SMA) was occluded for 45 minutes, and at the start of reperfusion MSCs were injected into the submucosa of the small bowel intestine. Treatment of the small bowel with MSC decreased the severity of intestinal barrier injury, bacterial translocation and serum lactate levels in this study. Given the preponderance of evidence supporting the potential therapeutic roles for MSCs with respect to other organ systems, the authors are to be commended for pursuing this line of investigation with respect to the small bowel. In light of the observed beneficial effects of MSC treatment on the bowel, there are many questions to be answered. For instance what is the mechanism by which MSCs exert their salutary effects, and how can we clinically deliver these MSCs? What would be the effects of a pre-ischemic strategy compared to a post-ischemic strategy? Finally, what is the appropriate number of cells to deliver? Certainly some answers may be inferred from previous studies that indicate that MSCs produce potent trophic factors that are associated with increased angiogenesis and decreased apoptosis [6]. However, the current study did not examine cytokine levels in the bowel after I/R. It is likely given the improved gut integrity in the treatment group as well as the histologic data that apoptosis is decreased in this study. Nonetheless, this supposition and other possible associations need to be more rigourously tested in future experiments. Bowel I/R is encountered in multiple clinical scenarios such as necrotizing enterocolitis, trauma, cardiac surgery, sepsis, abdominal aortic surgery, strangulated hernias and bowel transplantation. To date, numerous pathways have been linked to the injury related to bowel I/R [9]. Thus it is likely that a therapeutic strategy for bowel I/R will be multi-factorial. As the understanding of MSC biology continues to evolve, the role of these cells may indeed be promising for combating the devastating effects of intestinal I/R injury.
Ventricular Myosin Light Chain-2 Gene Expression in Developing Heart of Chicken Embryos

Recent gene knock-out studies in mice have suggested that ventricular myosin light chain-2 (vMLC2) has a role in the regulation of cardiogenic development and that perturbation in expression of vMLC2 is linked to the onset of dilated cardiomyopathy. In an attempt to develop an avian model for such studies, we examined the expression pattern of vMLC2 in chicken embryos at various stages and analyzed the effect of antisense oligonucleotide-mediated interference of vMLC2 function in cultures of whole embryos. Our results showed vMLC2 to be a specific marker for ventricular chamber throughout chicken embryonic development and antisense vMLC2 treatment of primitive streak stage (stage 4) embryos to produce pronounced dilation of heart tube with severe deficiency in formation of striated myofibrils. Further studies with antisense mRNA techniques of whole embryo cultures should, therefore, be useful to evaluate the role of vMLC2 and other putative regulatory factors in cardiac myofibrillogenesis
Variation in Variables that Predict Progression from MCI to AD Dementia over Duration of Follow-up.

The purpose of this paper is to investigate the relative utility of using neuroimaging, genetic, cerebrospinal fluid (CSF), and cognitive measures to predict progression from mild cognitive impairment (MCI) to Alzheimer's disease (AD) dementia over a follow-up period. The studied subjects were 139 persons with MCI enrolled in the Alzheimer's Disease Neuroimaging Initiative. Predictors of progression to AD included brain volume, ventricular volume, hippocampal volume, APOE e4 two alleles, Aβ42, p-tau181, p-tau181/Aβ42, memory, language, and executive function. We employ a combination of Cox regression analyses and time-dependent receiver operating characteristic (ROC) methods to assess the prognostic utility and performance stability of candidate biomarkers. In a demographic-adjusted multivariable Cox model, seven measures- brain volume, hippocampal volume, ventricular volume, APOE e4 two alleles, Aβ42, Memory composite, Executive function composite - predicted progression to AD. Time-dependent ROC revealed that this multivariable model had an area under the curve of 0.832, 0.788, 0.794, and 0.757 at 12, 18, 24, and 36 months respectively. Supplemental Cox models with time of origin set differentially at 12, 18, 24 and 36 months showed that six measures were significant predictors at 12 months whereas only memory and executive function predicted progression to AD at 18 and 24 months. The authors concluded that baseline volumetric MRI and cognitive measures selectively predict progression from MCI to AD, with cognitive measures remaining predictive even late in the follow-up period. These findings may inform case selection for AD clinical trials.
Pancreatic Endoplasmic Reticulum Kinase Activation Promotes Medulloblastoma Cell Migration and Invasion through Induction of Vascular Endothelial Growth Factor A

Evidence is accumulating that activation of the pancreatic endoplasmic reticulum kinase (PERK) in response to endoplasmic reticulum (ER) stress adapts tumor cells to the tumor microenvironment and enhances tumor angiogenesis by inducing vascular endothelial growth factor A (VEGF-A). Recent studies suggest that VEGF-A can act directly on certain tumor cell types in an autocrine manner, via binding to VEGF receptor 2 (VEGFR2), to promote tumor cell migration and invasion. Although several reports show that PERK activation increases VEGF-A expression in medulloblastoma, the most common solid malignancy of childhood, the role that either PERK or VEGF-A plays in medulloblastoma remains elusive. In this study, we mimicked the moderate enhancement of PERK activity observed in tumor patients using a genetic approach and a pharmacologic approach, and found that moderate activation of PERK signaling facilitated medulloblastoma cell migration and invasion and increased the production of VEGF-A. Moreover, using the VEGFR2 inhibitor SU5416 and the VEGF-A neutralizing antibody to block VEGF-A/VEGFR2 signaling, our results suggested that tumor cell-derived VEGF-A promoted medulloblastoma cell migration and invasion through VEGFR2 signaling, and that both VEGF-A and VEGFR2 were required for the promoting effects of PERK activation on medulloblastoma cell migration and invasion. Thus, these findings suggest that moderate PERK activation promotes medulloblastoma cell migration and invasion through enhancement of VEGF-A/VEGFR2 signaling.
ALTDSE: An Arnoldi-Lanczos program to solve the time-dependent Schrödinger equation

Abstract We describe a general ab initio and non-perturbative method to solve the time-dependent Schrodinger equation (TDSE) for the interaction of a strong attosecond laser pulse with a general atom. While the field-free Hamiltonian and the dipole matrices may be generated using an arbitrary primitive basis, they are assumed to have been transformed to the eigenbasis of the problem before the solution of the TDSE is propagated in time using the Arnoldi–Lanczos method. Probabilities for survival of the ground state, excitation, and single ionization can be extracted from the propagated wavefunction. Program summary Program title: ALTDSE Catalogue identifier: AEDM_v1_0 Program summary URL: http://cpc.cs.qub.ac.uk/summaries/AEDM_v1_0.html Program obtainable from: CPC Program Library, Queen's University, Belfast, N. Ireland Licensing provisions: Standard CPC licence, http://cpc.cs.qub.ac.uk/licence/licence.html No. of lines in distributed program, including test data, etc.: 2154 No. of bytes in distributed program, including test data, etc.: 30 827 Distribution format: tar.gz Programming language: Fortran 95. [A Fortran 2003 call to “flush” is used to simplify monitoring the output file during execution. If this function is not available, these statements should be commented out.]. Computer: Shared-memory machines Operating system: Linux, OpenMP Has the code been vectorized or parallelized?: Yes RAM: Several Gb, depending on matrix size and number of processors Supplementary material: To facilitate the execution of the program, Hamiltonian field-free and dipole matrix files are provided. Classification: 2.5 External routines: LAPACK, BLAS Nature of problem: We describe a computer program for a general ab initio and non-perturbative method to solve the time-dependent Schrodinger equation (TDSE) for the interaction of a strong attosecond laser pulse with a general atom [1,2]. The probabilities for survival of the initial state, excitation of discrete states, and single ionization due to multi-photon processes can be obtained. Solution method: The solution of the TDSE is propagated in time using the Arnoldi–Lanczos method. The field-free Hamiltonian and the dipole matrices, originally generated in an arbitrary basis (e.g., the flexible B -spline R -matrix (BSR) method with non-orthogonal orbitals [3]), must be provided in the eigenbasis of the problem as input. Restrictions: The present program is restricted to a 1 S e initial state and linearly polarized light. This is the most common situation experimentally, but a generalization is straightforward. Running time: Several hours, depending on the number of threads used. References: [1] X. Guan, O. Zatsarinny, K. Bartschat, B.I. Schneider, J. Feist, C.J. Noble, Phys. Rev. A 76 (2007) 053411. [2] X. Guan, C.J. Noble, O. Zatsarinny, K. Bartschat, B.I. Schneider, Phys. Rev. A 78 (2008) 053402. [3] O. Zatsarinny, Comput. Phys. Comm. 174 (2006) 273.
Analyzing the impact of the N-policy on Quality of Service in wireless sensor networks

Energy conservation in wireless sensor networks (WSN) has gained the attention of several research efforts. Several techniques have been proposed to optimize power consumption, and hence increasing network life time, by focusing on different aspects of the functions of a single wireless sensor node such as data aggregation, efficient routing, sleep/wake scheduling, and buffer management. One of the techniques proposed to optimize power consumption in wireless sensor nodes is based on the N-policy which reduces the number of times the radio channel transitions from the off to the on state. Although the impact of the N-policy on power conservation in wireless sensor networks has been verified by several research efforts, the impact of this policy on the Quality of Service (QoS) was never investigated thoroughly especially for applications where end-to-end delay is crucial to the overall performance of the application. In this paper, we analyze the impact of the N-policy on the queuing delay for wireless sensor networks applications that are sensitive to delay. We investigate if there exists an optimal queue length N that can minimize power consumption as well as satisfy the required delay at the same time.
Effects of alternatives in coalition bargaining

Abstract A critical factor in bargaining and coalition formation is the alternative outcomes of the bargainers if an agreement cannot be reached. In some situations bargainers have individual alternatives while in other situations their alternatives must be negotiated with others. The purpose of this study was to contrast the effects of one-person and two-person alternatives on coalition outcomes. The second purpose of the study was to contrast the predictions of four theories of coalition formation: bargaining theory, equal excess model, Shapley value, and a special case of equity theory. The results indicate that one-person alternatives enhance the bargaining strength of the stronger players more than two-person alternatives. The predictions of the equal excess model and the Shapley value were more accurate than the predictions of bargaining theory and equity theory. However, the greater accuracy of the equal excess model and the Shapley value may be restricted to situations in which the bargainers have one-person rather than two-person alternatives.
SU-E-T-185: Passing Rates of 83 Patient-Specific IMRT QA Measurements with ArcCHECK Using Various Gamma Criteria

Purpose: Three‐dimensional diode arrays are an important tool in patient‐specific intensity modulated radiotherapyquality assurance(IMRT QA) for arc therapy. We investigated the results of 83 patient‐specific IMRT QA measurements made on TomoTherapy using the Sun Nuclear ArcCHECK. Methods: Our ArcCHECK setup consists of a water‐equivalent plug and ion chamber at the center of the device. Planned dose is recalculated for ArcCHECK using the TomoTherapy planning workstation on the “Normal” setting creating dose voxels sized 4.8mm in each dimension. Patient‐specific IMRT QA measurements are made for all patients on TomoTherapy using megavoltage computed tomography to register the device. Analysis is performed in Sun Nuclear's MapCHECK software using various dose difference and distance gamma criteria using absolute dose (AD). The average passing rates, uncertainty, and upper/lower quartiles (UQ and LQ) of the data were computed. Four measurements deemed unacceptable were left in the data to determine the number of false negatives (FN) and false positives (FP) given when using various passing thresholds. Results: The average passing rates using gamma criteria 5%/5mm, 5%/3mm, 3%/5mm, 3%/3mm, 2%/5mm, 2%/3mm, 1%/5mm and 1%/3mm were 99.7 +/−0.5%, 98.4 +/−1.9%, 98.6 +/−1.5%, 94.9 +/−3.5%, 97.0 +/2.5%, 90.4 +/−5.1%, 94.1 +/−4.6% and 83.6 +/−7.1% respectively. The distribution of points passing using 2%/5mm (UQ 98.8 LQ 95.8) was significantly better than the typical criteria of 3%/3mm (UQ 97.8 LQ 92.7). 2%/5mm were the only criteria that gave no FN or FP using a percentage of points passing threshold of 93%. At this threshold 3%/3mm produced 21 FN and 1 FP. Conclusions: The performance of various criteria at or below the 3% dose difference threshold demonstrates improved results using 5mm as the distance parameter. This is likely due to the “Normal” dose voxel size in TomoTherapy and has led us to investigate using the “Fine” dose grid of 2.4mm.
Development and verification of an agent-based model of opinion leadership

The use of opinion leaders is a strategy used to speed the process of translating research into practice. Much is still unknown about opinion leader attributes and activities and the context in which they are most effective. Agent-based modeling is a methodological tool that enables demonstration of the interactive and dynamic effects of individuals and their behaviors on other individuals in the environment. The purpose of this study was to develop and test an agent-based model of opinion leadership. The details of the design and verification of the model are presented. The agent-based model was developed by using a software development platform to translate an underlying conceptual model of opinion leadership into a computer model. Individual agent attributes (for example, motives and credibility) and behaviors (seeking or providing an opinion) were specified as variables in the model in the context of a fictitious patient care unit. The verification process was designed to test whether or not the agent-based model was capable of reproducing the conditions of the preliminary conceptual model. The verification methods included iterative programmatic testing (`debugging’) and exploratory analysis of simulated data obtained from execution of the model. The simulation tests included a parameter sweep, in which the model input variables were adjusted systematically followed by an individual time series experiment. Statistical analysis of model output for the 288 possible simulation scenarios in the parameter sweep revealed that the agent-based model was performing, consistent with the posited relationships in the underlying model. Nurse opinion leaders act on the strength of their beliefs and as a result, become an opinion resource for their uncertain colleagues, depending on their perceived credibility. Over time, some nurses consistently act as this type of resource and have the potential to emerge as opinion leaders in a context where uncertainty exists. The development and testing of agent-based models is an iterative process. The opinion leader model presented here provides a basic structure for continued model development, ongoing verification, and the establishment of validation procedures, including empirical data collection.